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of special interest. This well written review from the Mitchinson laboratory summarizes the recent findings on actin dynamics in lamellipodia. The authors discuss the role of several proteins regulating actin polymerization, depolymerization, and retrograde flow.
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Welch MD, Mallavarapu A, Rosenblatt J, Mitchison TJ. Actin dynamics in vivo. of special interest Curr Opin Cell Biol. 9:1997;54-61 This well written review from the Mitchinson laboratory summarizes the recent findings on actin dynamics in lamellipodia. The authors discuss the role of several proteins regulating actin polymerization, depolymerization, and retrograde flow.
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Actin polymerization is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes
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of outstanding interest. A seven-subunit complex was purified from cytoskeletal extracts from human platelets and demonstrated to be sufficient to induce actin polymerization at the surface of Listeria monocytogenes. Two of the seven subunits have been identified as Arp2 and Arp3 proteins by peptide sequencing.
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Welch MD, Iwamatsu A, Mitchison TJ. Actin polymerization is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes. of outstanding interest Nature. 385:1997;265-269 A seven-subunit complex was purified from cytoskeletal extracts from human platelets and demonstrated to be sufficient to induce actin polymerization at the surface of Listeria monocytogenes. Two of the seven subunits have been identified as Arp2 and Arp3 proteins by peptide sequencing.
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Welch, M.D.1
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Profilin interacts with the Gly-Pro-Pro-Pro-Pro-Pro sequences of vasodilator-stimulated phosphoprotein (VASP): Implications for actin-based Listeria motility
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0030592559
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Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics
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of outstanding interest. Mena and Evl have been identified as two murine homologues of Drosophila Enabled, which is required for the formation of proper axonal connections. Focusing on Mena, the authors show that this VASP-related protein localizes to focal contacts, binds profilin, and is recruited to the surface of Listeria monocytogenes in infected cells. Most importantly, expression of neuronal-enriched Mena isoforms in fibroblasts results in the formation of actin-rich protrusions.
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Gertler FB, Niebuhr K, Reinhard M, Wehland J, Soriano P. Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics. of outstanding interest Cell. 87:1996;227-239 Mena and Evl have been identified as two murine homologues of Drosophila Enabled, which is required for the formation of proper axonal connections. Focusing on Mena, the authors show that this VASP-related protein localizes to focal contacts, binds profilin, and is recruited to the surface of Listeria monocytogenes in infected cells. Most importantly, expression of neuronal-enriched Mena isoforms in fibroblasts results in the formation of actin-rich protrusions.
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An Aplysia cell adhesion molecule associated with site-directed actin filament assembly in neuronal growth cones
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of special interest. For the first time, a member of the Ig superfamily, apCAM, is shown to trigger actin assembly. Interestingly, this Aplysia NCAM (neural CAM) homologue associates in different ways with the underlying actin cytoskeleton depending on the crosslinking density.
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0029863153
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Myosin drives retrograde F-actin flow in neuronal growth cones
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of outstanding interest. The first evidence that myosin motor action drives retrograde F-actin flow in neuronal growth cones. Two different approaches have been used to inhibit myosin function: injection of NEM-inactivated myosin S1 fragments into cultured neurons and pharmacological treatment with BDM. In combination with cytochalasin experiments. The results demonstrate that growth is regulated by both actomyosin motility and actin polymerization.
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Lin C-H, Espreafico EM, Mooseker MS, Forscher P. Myosin drives retrograde F-actin flow in neuronal growth cones. of outstanding interest Neuron. 16:1996;769-782 The first evidence that myosin motor action drives retrograde F-actin flow in neuronal growth cones. Two different approaches have been used to inhibit myosin function: injection of NEM-inactivated myosin S1 fragments into cultured neurons and pharmacological treatment with BDM. In combination with cytochalasin experiments. The results demonstrate that growth is regulated by both actomyosin motility and actin polymerization.
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Lin C-H1
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of special interest. The function of cofilin in actin depolymerization was analyzed in yeast strains expressing cofilin mutants generated by site-directed mutagenesis. Interestingly, endocytosis, but not cortical actin patch motility, was reported to be affected in these cofilin mutants, suggesting that the former but not the latter pocess in dependent on actin filament turnover.
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Lappalainen P, Drubin DG. Cofilin promotes rapid actin filament turnover in vivo. of special interest Nature. 388:1997;78-82 The function of cofilin in actin depolymerization was analyzed in yeast strains expressing cofilin mutants generated by site-directed mutagenesis. Interestingly, endocytosis, but not cortical actin patch motility, was reported to be affected in these cofilin mutants, suggesting that the former but not the latter pocess in dependent on actin filament turnover.
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Lappalainen, P.1
Drubin, D.G.2
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Rosenblatt J, Agnew BJ, Abe H, Bamburg JR, Mitchison TJ. Xenopus actin depolymerizing factor/cofilin (XAC) is responsible for the turnover of actin filaments in Listeria monocytogenes tails. J Cell Biol. 136:1997;1323-1332.
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Rosenblatt, J.1
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0029815611
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2-dependent manner downstream of tyrosine kinases
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2-binding and actin-depolymerization activity. In addition, the data suggest that N-WASP mediates EGF-induced rearrangement of the actin cytoskeleton.
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2-binding and actin-depolymerization activity. In addition, the data suggest that N-WASP mediates EGF-induced rearrangement of the actin cytoskeleton.
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of special interest. This detailed study from the Bridgman laboratory demonstrates that low doses of nocodazole decrease both dynamic properties of microtubule ends and axon extension rates, but not microtubule mass. The analysis of the light and electron microscopy data suggests that dynamic microtubules are required for axonal extension and support the findings of a previous report [28].
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Microtubule-associated protein 2c reorganizes both microtubules and microfilaments into distinct cytological structures in an actin-binding protein-280-deficient melanoma cell line
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of outstanding interest. Another excellent study from the Borisy laboratory on the localization of cytoskeletal elements in motile cells. In addition to ultrastructural data on the actin - myosin II system of keratocytes, analysis of myosin dynamics support a hypothesis of dynamic network contraction as a mechanism for cell body translocation.
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Svitkina TM, Verkhovsky AB, McQuade KM, Borisy GG. Analysis of the actin-myosin II system in fish epidermal keratocytes - mechanism of cell body translocation. of outstanding interest J Cell Biol. 139:1997;397-415 Another excellent study from the Borisy laboratory on the localization of cytoskeletal elements in motile cells. In addition to ultrastructural data on the actin - myosin II system of keratocytes, analysis of myosin dynamics support a hypothesis of dynamic network contraction as a mechanism for cell body translocation.
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0030727892
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of outstanding interest. Using elegant photoactivation of fluorescent microtuble-marking techniques and time lapse imaging, Waterman-Storer and Salmon provide several important new insights into microtubule dynamics in migrating cells. Marking experiments revealed that microbules in the lamella move towards the cell body at the speed of retrograde flow by an actomyosin-dependent mechanism. In addition, retrograde F-actin flow was found to attenuate microtubule growth, quench dynamic instability and enhance microtubule breakage. The latter effect often generated short microtubules fragments that could translocate by subunit treadmilling.
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Waterman-Storer CM, Salmon ED. Actomyosin-based retrograde flow of microtubules in the lamella of migrating epithelial cells influences microtubule dynamic instability and turnover and is associated with microtubule breakage and treadmilling. of outstanding interest J Cell Biol. 139:1997;417-434 Using elegant photoactivation of fluorescent microtuble-marking techniques and time lapse imaging, Waterman-Storer and Salmon provide several important new insights into microtubule dynamics in migrating cells. Marking experiments revealed that microbules in the lamella move towards the cell body at the speed of retrograde flow by an actomyosin-dependent mechanism. In addition, retrograde F-actin flow was found to attenuate microtubule growth, quench dynamic instability and enhance microtubule breakage. The latter effect often generated short microtubules fragments that could translocate by subunit treadmilling.
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Suter DM, Errante LD, Belotserkovsky V, Forscher P. The Ig superfamily cell adhesion molecule apCAM mediates growth cone steering by substrate - cytoskeletal coupling. of special interest J Cell Biol. 141:1998; The authors provide strong evidence that the Aplysia cell adhesion molecule apCAM can mediate growth cone advance and steering by a mechanism involving substrate - cytoskeletal coupling. A novel assay was used in which beads derivatized with specific molecuar substrates were restrained from retrograde translocation, resulting in a build up of tension between the restrained bead and the moving actin cytoskeleton. Build up of tension was correlated with directed axonal microtubule advance.
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The 180-kD component of the neural cell adhesion molecule N-CAM is involved in a cell-cell contacts and cytoskeleton-membrane interactions
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49
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Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites
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of special interest. Expression of neuroglian in Drosophila S2 cells leads to cell aggregation by homophilic neuroglian interactions and to recruitment of ankyrin to sites of cell - cell contact, whereas non-interacting plasma membranes are devoid of ankyrin. These results suggest that homophilic cell - cell adhesion is necessary to target ankyrin to L1-like CAMs.
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Dubreuil RR, MacVicar G, Dissanayake S, Liu C, Homer D, Hortsch M. Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites. of special interest J Cell Biol. 133:1996;647-655 Expression of neuroglian in Drosophila S2 cells leads to cell aggregation by homophilic neuroglian interactions and to recruitment of ankyrin to sites of cell - cell contact, whereas non-interacting plasma membranes are devoid of ankyrin. These results suggest that homophilic cell - cell adhesion is necessary to target ankyrin to L1-like CAMs.
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Dubreuil, R.R.1
MacVicar, G.2
Dissanayake, S.3
Liu, C.4
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Hortsch, M.6
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50
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0031006110
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Tyrosine phosphorylation at a site highly conserved in the L1 family of cell adhesion molecules abolishes ankyrin binding and increases lateral mobility of neurofascin
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of outstanding interest. This excellent work presents evidence that tyrosine phosphorylation of neurofascin at a site conserved among L1 family members affects the interaction between neurofascin and ankyrin, providing a mechanism for the regulation of CAM - cytoskeleton interactions.
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Garver TD, Ren Q, Tuvia S, Bennett V. Tyrosine phosphorylation at a site highly conserved in the L1 family of cell adhesion molecules abolishes ankyrin binding and increases lateral mobility of neurofascin. of outstanding interest J Cell Biol. 137:1997;703-714 This excellent work presents evidence that tyrosine phosphorylation of neurofascin at a site conserved among L1 family members affects the interaction between neurofascin and ankyrin, providing a mechanism for the regulation of CAM - cytoskeleton interactions.
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J Cell Biol
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Garver, T.D.1
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Bennett, V.4
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51
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Integrin function: Molecular hierarchies of cytoskeletal and signaling molecules
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Miyamoto S, Teramoto H, Coso OA, Gutkind JS, Burbelo PD, Akiyama SK, Yamada KM. Integrin function: molecular hierarchies of cytoskeletal and signaling molecules. J Cell Biol. 131:1995;791-805.
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Schmidt CE, Dai J, Lauffenburger DA, Sheetz MP, Horwitz AF. Integrin-cytoskeletal interactions in neuronal growth cones. J Neurosci. 15:1995;3400-3407.
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53
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0029740182
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Ligand binding regulates the directed movement of beta1 integrins on fibroblasts
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of special interest. The movement of fibronectin or β1 integrin antibody-coated gold particles on fibroblasts was analyzed using nanometer-resolution tracking techniques. The addition of RGD-containing peptides caused directed movements of antibody-coated beads, suggesting that ligand binding is an important step in the process of integrin - cytoskeleton association.
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Felsenfeld DP, Choquet D, Sheetz MP. Ligand binding regulates the directed movement of beta1 integrins on fibroblasts. of special interest Nature. 383:1996;438-440 The movement of fibronectin or β1 integrin antibody-coated gold particles on fibroblasts was analyzed using nanometer-resolution tracking techniques. The addition of RGD-containing peptides caused directed movements of antibody-coated beads, suggesting that ligand binding is an important step in the process of integrin - cytoskeleton association.
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Nature
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Felsenfeld, D.P.1
Choquet, D.2
Sheetz, M.P.3
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54
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0030994017
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Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages
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of special interest. of outstanding interest. Using similar tools to those used in [53], the authors clearly demonstrate that application of external forces influences the strength of integrin - cytoskeleton linkages. This work provides important biophysical evidence that cells are able to sense the rigidity of the extracellular matrix.
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of special interest Choquet D, Felsenfeld DP, Sheetz MP. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. of outstanding interest Cell. 88:1997;39-48 Using similar tools to those used in [53], the authors clearly demonstrate that application of external forces influences the strength of integrin - cytoskeleton linkages. This work provides important biophysical evidence that cells are able to sense the rigidity of the extracellular matrix.
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Cell
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Choquet, D.1
Felsenfeld, D.P.2
Sheetz, M.P.3
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55
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Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia
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Nobes CD, Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 81:1995;53-62.
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Nobes, C.D.1
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56
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9444242736
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Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)
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Kimura K, Ito M, Amano M, Chihara K, Fukata Y, Nakafuku M, Yamamori B, Feng J, Nakano T, Okawa K, et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science. 273:1996;245-248.
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Kimura, K.1
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57
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0029995797
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Rho-stimulated contractility drives the formation of stress fibers and focal adhesions
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of special interest. The authors provide evidence for an interesting pathway whereby Rho-medicated contractility induces the formation of stress fibers and focal adhesions. They propose that Rho affects contractility by regulation of myosin light-chain phosphorylation.
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Chrzanowska-Wodnicka M, Burridge K. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. of special interest J Cell Biol. 133:1996;1403-1415 The authors provide evidence for an interesting pathway whereby Rho-medicated contractility induces the formation of stress fibers and focal adhesions. They propose that Rho affects contractility by regulation of myosin light-chain phosphorylation.
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Chrzanowska-Wodnicka, M.1
Burridge, K.2
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58
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0030221511
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CAMP-FGF receptor interactions: A model for axonal growth
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of special interest. This well-written review discusses evidence for a model suggesting that CAMs, such as NCAM, L1 and cadherin, mediate neurite outgrowth by activation of the FGF receptor, which, in turn, activates a PLCγ-dependent signaling cascade. Considerations of binding motifs based on structural analysis provide further support for this model.
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Doherty P, Walsh FS. CAMP-FGF receptor interactions: a model for axonal growth. of special interest Mol Cell Neurosci. 8:1996;99-111 This well-written review discusses evidence for a model suggesting that CAMs, such as NCAM, L1 and cadherin, mediate neurite outgrowth by activation of the FGF receptor, which, in turn, activates a PLCγ-dependent signaling cascade. Considerations of binding motifs based on structural analysis provide further support for this model.
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Mol Cell Neurosci
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Doherty, P.1
Walsh, F.S.2
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59
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0031039771
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Expression of a dominant negative FGF receptor inhibits axonal growth and FGF receptor phosphorylation stimulated by CAMs
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of outstanding interest. The strongest evidence to date for the signaling pathway discussed in [58]. Neurite outgrowth mediated by NCAM, L1 and N-cadherin was abolished in PC12 cells or primary neurons from transgenic mice expressing a kinase-deleted dominant-negative form of the FGF receptor. Addition of soluble NCAM- and L1-Fc chimera resulted in phosphorylation of the FGF receptor - a key step in receptor activation.
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Saffell JL, Williams EJ, Mason IJ, Walsh FS, Doherty P. Expression of a dominant negative FGF receptor inhibits axonal growth and FGF receptor phosphorylation stimulated by CAMs. of outstanding interest Neuron. 18:1997;231-242 The strongest evidence to date for the signaling pathway discussed in [58]. Neurite outgrowth mediated by NCAM, L1 and N-cadherin was abolished in PC12 cells or primary neurons from transgenic mice expressing a kinase-deleted dominant-negative form of the FGF receptor. Addition of soluble NCAM- and L1-Fc chimera resulted in phosphorylation of the FGF receptor - a key step in receptor activation.
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(1997)
Neuron
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, pp. 231-242
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Saffell, J.L.1
Williams, E.J.2
Mason, I.J.3
Walsh, F.S.4
Doherty, P.5
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60
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Selective neural cell adhesion molecule signaling by Src family tyrosine kinases and tyrosine phosphatases
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Maness PF, Beggs HE, Klinz SG, Morse WR. Selective neural cell adhesion molecule signaling by Src family tyrosine kinases and tyrosine phosphatases. Perspect Dev Neurobiol. 4:1996;169-181.
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Maness, P.F.1
Beggs, H.E.2
Klinz, S.G.3
Morse, W.R.4
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61
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0029662193
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Intracellular signaling is changed after clustering of the neural cell adhesion molecules axonin-1 and NgCAM during neurite fasciculation
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Kunz S, Ziegler U, Kunz B, Sonderegger P. Intracellular signaling is changed after clustering of the neural cell adhesion molecules axonin-1 and NgCAM during neurite fasciculation. J Cell Biol. 135:1996;253-267.
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Kunz, S.1
Ziegler, U.2
Kunz, B.3
Sonderegger, P.4
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62
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Involvement of p90rsk in neurite outgrowth mediated by the cell adhesion molecule L1
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Wong EV, Schaefer AW, Landreth G, Lemmon V. Involvement of p90rsk in neurite outgrowth mediated by the cell adhesion molecule L1. J Biol Chem. 271:1996;18217-18223.
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Wong, E.V.1
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Landreth, G.3
Lemmon, V.4
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63
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0030887348
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NCAM140 interacts with the focal adhesion kinase p125(fak) and the SRC-related tyrosine kinase p59(fyn)
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of special interest. Immunoprecipitation studies revealed that the NCAM140 isoform is associated with the nonreceptor tyrosine kinases p59fyn and p125fak, which are known to be involved in integrin-dependent signaling. Although the role of p125fak in growth cone guidance remains to be established, this kinase could provide a means of integrating signal transduction pathways associated with lg CAM and integrin receptors.
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Beggs HE, Baragona SC, Hemperly JJ, Maness PF. NCAM140 interacts with the focal adhesion kinase p125(fak) and the SRC-related tyrosine kinase p59(fyn). of special interest J Biol Chem. 272:1997;8310-8319 Immunoprecipitation studies revealed that the NCAM140 isoform is associated with the nonreceptor tyrosine kinases p59fyn and p125fak, which are known to be involved in integrin-dependent signaling. Although the role of p125fak in growth cone guidance remains to be established, this kinase could provide a means of integrating signal transduction pathways associated with lg CAM and integrin receptors.
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J Biol Chem
, vol.272
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Beggs, H.E.1
Baragona, S.C.2
Hemperly, J.J.3
Maness, P.F.4
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Neural cell adhesion molecule L1: Signaling pathways and growth cone motility
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Kamiguchi H, Lemmon V. Neural cell adhesion molecule L1: signaling pathways and growth cone motility. J Neurosci Res. 49:1997;1-8.
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Phosphoinositides and calcium as regulators of cellular actin assembly and disassembly
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Janmey PA. Phosphoinositides and calcium as regulators of cellular actin assembly and disassembly. Annu Rev Physiol. 56:1994;169-191.
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A role for gelsolin in actuating epidermal growth factor receptor-mediated cell motility
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2, making it available for actin turnover.
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Chen, P.1
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67
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Pollard, T.D.5
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68
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Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein
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of special interest. A genetic screen for defects in photoreceptor axon guidance led to the identification of the Dreadlocks SH2/SH3 adapter protein, which could provide a link between tyrosine phosphorylation and cytoskeletal regulatory proteins.
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Garrity PA, Rao Y, Salecker I, McGlade J, Pawson T, Zipursky SL. Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein. of special interest Cell. 85:1996;639-650 A genetic screen for defects in photoreceptor axon guidance led to the identification of the Dreadlocks SH2/SH3 adapter protein, which could provide a link between tyrosine phosphorylation and cytoskeletal regulatory proteins.
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(1996)
Cell
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Garrity, P.A.1
Rao, Y.2
Salecker, I.3
McGlade, J.4
Pawson, T.5
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69
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Luo L, Jan LY, Jan YN. Rho family small GTP-binding proteins in growth cone signalling. Curr Opin Neurobiol. 7:1997;81-86.
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70
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Rho family GTPases and neuronal growth cone remodelling: Relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid
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Kozma R, Sarner S, Ahmed S, Lim L. Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid. Mol Cell Biol. 17:1997;1201-1211.
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Kozma, R.1
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71
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Inhibition of lysophosphatidate- And thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho
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Jalink K, van Corven EJ, Hengeveld T, Morii N, Narumiya S, Moolenaar WH. Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho. J Cell Biol. 126:1994;801-810.
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72
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0030929149
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Identification of a novel, putative Rho-specific GDP/GTP exchange factor and a RhoA-binding protein: Control of neuronal morphology
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of special interest. Two novel regulators of RhoA involved in neurite contractility and outgrowth have been identified: a putative RhoA-activating nucleotide exchange factor inducing neurite retraction and negative regulator of RhoA-promoting neurite outgrowth.
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Gebbink MF, Kranenburg O, Poland M, van Horck FP, Houssa B, Moolenaar WH. Identification of a novel, putative Rho-specific GDP/GTP exchange factor and a RhoA-binding protein: control of neuronal morphology. of special interest J Cell Biol. 137:1997;1603-1613 Two novel regulators of RhoA involved in neurite contractility and outgrowth have been identified: a putative RhoA-activating nucleotide exchange factor inducing neurite retraction and negative regulator of RhoA-promoting neurite outgrowth.
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(1997)
J Cell Biol
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Gebbink, M.F.1
Kranenburg, O.2
Poland, M.3
Van Horck, F.P.4
Houssa, B.5
Moolenaar, W.H.6
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73
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Rac1 mediates collapsin-1-induced growth cone collapse
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Jin Z, Strittmatter SM. Rac1 mediates collapsin-1-induced growth cone collapse. J Neurosci. 17:1997;6256-6263.
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Jin, Z.1
Strittmatter, S.M.2
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74
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0030026182
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Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines
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of special interest. Expression of a constitutively active form of Rac1 in transgenic mice causes different effects on Purkinje cell axon terminals, dendritic trunks and spines, suggesting that establishment of different neuronal compartments may involve distinct mechanisms.
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Luo L, Hensch TK, Ackerman L, Barbel S, Jan LY, Jan YN. Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines. of special interest Nature. 379:1996;837-840 Expression of a constitutively active form of Rac1 in transgenic mice causes different effects on Purkinje cell axon terminals, dendritic trunks and spines, suggesting that establishment of different neuronal compartments may involve distinct mechanisms.
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Nature
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Luo, L.1
Hensch, T.K.2
Ackerman, L.3
Barbel, S.4
Jan, L.Y.5
Jan, Y.N.6
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75
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0030982564
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Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42
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of special interest. This in vitro study shows that all three Rho-related GTPases (Rho, Rac and Cdc42) are involved in dendritic growth and remodeling of cortical neurons, suggesting an important role of these regulatory proteins for the development of the cortex.
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Threadgill R, Bobb K, Ghosh A. Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42. of special interest Neuron. 19:1997;625-634 This in vitro study shows that all three Rho-related GTPases (Rho, Rac and Cdc42) are involved in dendritic growth and remodeling of cortical neurons, suggesting an important role of these regulatory proteins for the development of the cortex.
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(1997)
Neuron
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, pp. 625-634
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Threadgill, R.1
Bobb, K.2
Ghosh, A.3
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