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Volumn 18, Issue 1, 2008, Pages 69-76

Building a synapse: lessons on synaptic specificity and presynaptic assembly from the nematode C. elegans

Author keywords

[No Author keywords available]

Indexed keywords

CAENORHABDITIS ELEGANS; CELL ADHESION; ENDOCYTOSIS; GENETIC SCREENING; MOLECULAR INTERACTION; NEMATODE; NERVE CELL DIFFERENTIATION; NONHUMAN; POLARIZATION; PRESYNAPTIC NERVE; PRIORITY JOURNAL; REVIEW; SYNAPSE VESICLE; SYNAPTIC MEMBRANE; UBIQUITINATION;

EID: 46549083253     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.conb.2008.04.003     Document Type: Review
Times cited : (31)

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    • Grill B., Bienvenut W.V., Brown H.M., Ackley B.D., Quadroni M., and Jin Y. C. elegans RPM-1 regulates axon termination and synaptogenesis through the Rab GEF GLO-4 and the Rab GTPase GLO-1. Neuron 55 (2007) 587-601. The authors use a proteomic screen and functional genetic analysis to identify the RPM-1 binding partner, GLO-4. GLO-4 is part of a linear pathway including the Rab GTPase, GLO-1, and AP-3. This pathway was found to specifically regulate late endosomes at presynaptic terminals. The authors show that RPM-1 positively regulates the GLO pathway, while silencing a MAP kinase cascade. In this way, RPM-1 acts as a key regulator of both axon termination and synapse formation through a common set of molecular mediators.
    • (2007) Neuron , vol.55 , pp. 587-601
    • Grill, B.1    Bienvenut, W.V.2    Brown, H.M.3    Ackley, B.D.4    Quadroni, M.5    Jin, Y.6
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    • Mutations in synaptojanin disrupt synaptic vesicle recycling
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    • (2000) J Cell Biol , vol.150 , pp. 589-600
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    • UNC-80 and the NCA ion channels contribute to endocytosis defects in synaptojanin mutants
    • Synaptojanin/UNC-26 is a lipid phosphatase that regulates endocytosis at the synapse, and the authors use an unbiased mutagenesis screen to identify suppressors of synaptojanin. These suppressors include mutants in the NCA ion channel, and two novel proteins, unc-80 and unc-79. unc-80 regulates NCA channel insertion into the plasma membrane via an unknown mechanism. These findings suggest that ion channel activity is intimately linked with endocytosis at the synapse.
    • Jospin M., Watanabe S., Joshi D., Young S., Hamming K., Thacker C., Snutch T.P., Jorgensen E.M., and Schuske K. UNC-80 and the NCA ion channels contribute to endocytosis defects in synaptojanin mutants. Curr Biol 17 (2007) 1595-1600. Synaptojanin/UNC-26 is a lipid phosphatase that regulates endocytosis at the synapse, and the authors use an unbiased mutagenesis screen to identify suppressors of synaptojanin. These suppressors include mutants in the NCA ion channel, and two novel proteins, unc-80 and unc-79. unc-80 regulates NCA channel insertion into the plasma membrane via an unknown mechanism. These findings suggest that ion channel activity is intimately linked with endocytosis at the synapse.
    • (2007) Curr Biol , vol.17 , pp. 1595-1600
    • Jospin, M.1    Watanabe, S.2    Joshi, D.3    Young, S.4    Hamming, K.5    Thacker, C.6    Snutch, T.P.7    Jorgensen, E.M.8    Schuske, K.9
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    • UNC-46 is required for trafficking of the vesicular GABA transporter
    • In this study, the authors identify the mechanism of how the vesicular GABA transporter (VGAT) is localized/sorted to synaptic vesicles. The authors identify a novel LAMP-like protein, UNC-46, that is localized to synapses. In unc-46 mutants, VGAT is no longer localized to synaptic vesicles and becomes diffuse throughout the axon. Likewise, GABA release is compromised in unc-46 mutants leading to locomotion defects that can be overcome by the overexpression of VGAT.
    • Schuske K., Palfreyman M.T., Watanabe S., and Jorgensen E.M. UNC-46 is required for trafficking of the vesicular GABA transporter. Nat Neurosci 10 (2007) 846-853. In this study, the authors identify the mechanism of how the vesicular GABA transporter (VGAT) is localized/sorted to synaptic vesicles. The authors identify a novel LAMP-like protein, UNC-46, that is localized to synapses. In unc-46 mutants, VGAT is no longer localized to synaptic vesicles and becomes diffuse throughout the axon. Likewise, GABA release is compromised in unc-46 mutants leading to locomotion defects that can be overcome by the overexpression of VGAT.
    • (2007) Nat Neurosci , vol.10 , pp. 846-853
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    • Hall D.H., and Hedgecock E.M. Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell 65 (1991) 837-847
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    • LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins
    • This study identified a novel protein kinase LRK-1 that is required for polarized localization of synaptic vesicle proteins in C. elegans neurons. In lrk-1 mutants, synaptic vesicle components localize to the tips of dendritic endings in addition to axons, in a manner dependent on the AP-1 μ1 clathrin adaptor unc-101. On the basis of localization of LRK-1 to the Golgi compartment, the authors propose that LRK-1 excludes SV proteins from dendrite-specific transport pathways in the Golgi.
    • Sakaguchi-Nakashima A., Meir J.Y., Jin Y., Matsumoto K., and Hisamoto N. LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins. Curr Biol 17 (2007) 592-598. This study identified a novel protein kinase LRK-1 that is required for polarized localization of synaptic vesicle proteins in C. elegans neurons. In lrk-1 mutants, synaptic vesicle components localize to the tips of dendritic endings in addition to axons, in a manner dependent on the AP-1 μ1 clathrin adaptor unc-101. On the basis of localization of LRK-1 to the Golgi compartment, the authors propose that LRK-1 excludes SV proteins from dendrite-specific transport pathways in the Golgi.
    • (2007) Curr Biol , vol.17 , pp. 592-598
    • Sakaguchi-Nakashima, A.1    Meir, J.Y.2    Jin, Y.3    Matsumoto, K.4    Hisamoto, N.5
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    • Inositol monophosphatase regulates localization of synaptic components and behavior in the mature nervous system of C. elegans
    • This study demonstrates that the inositol-producing enzyme, myo-inositol monophosphatase (IMPase), is required for the maintenance of neuronal polarity in the RIA thermotaxis neurons. The authors use a behavioral screen to identify mutants with thermotaxis phenotypes, and find that ttx-7/IMPase mutants are athermotactic and display mislocalization of presynaptic and postsynaptic proteins in the RIA neurons. Interestingly, both thermotaxis and synaptic protein defects in these neurons can be phenocopied by the administration of the IMPase inhibitor lithium, and rescued by exogenous inositol.
    • Tanizawa Y., Kuhara A., Inada H., Kodama E., Mizuno T., and Mori I. Inositol monophosphatase regulates localization of synaptic components and behavior in the mature nervous system of C. elegans. Genes Dev 20 (2006) 3296-3310. This study demonstrates that the inositol-producing enzyme, myo-inositol monophosphatase (IMPase), is required for the maintenance of neuronal polarity in the RIA thermotaxis neurons. The authors use a behavioral screen to identify mutants with thermotaxis phenotypes, and find that ttx-7/IMPase mutants are athermotactic and display mislocalization of presynaptic and postsynaptic proteins in the RIA neurons. Interestingly, both thermotaxis and synaptic protein defects in these neurons can be phenocopied by the administration of the IMPase inhibitor lithium, and rescued by exogenous inositol.
    • (2006) Genes Dev , vol.20 , pp. 3296-3310
    • Tanizawa, Y.1    Kuhara, A.2    Inada, H.3    Kodama, E.4    Mizuno, T.5    Mori, I.6
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    • Mammalian SAD kinases are required for neuronal polarization
    • Kishi M., Pan Y.A., Crump J.G., and Sanes J.R. Mammalian SAD kinases are required for neuronal polarization. Science 307 (2005) 929-932
    • (2005) Science , vol.307 , pp. 929-932
    • Kishi, M.1    Pan, Y.A.2    Crump, J.G.3    Sanes, J.R.4
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    • The short coiled-coil domain-containing protein UNC-69 cooperates with UNC-76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans
    • Su C.W., Tharin S., Jin Y., Wightman B., Spector M., Meili D., Tsung N., Rhiner C., Bourikas D., Stoeckli E., et al. The short coiled-coil domain-containing protein UNC-69 cooperates with UNC-76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans. J Biol 5 (2006) 9
    • (2006) J Biol , vol.5 , pp. 9
    • Su, C.W.1    Tharin, S.2    Jin, Y.3    Wightman, B.4    Spector, M.5    Meili, D.6    Tsung, N.7    Rhiner, C.8    Bourikas, D.9    Stoeckli, E.10
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    • Neuronal polarity is regulated by a direct interaction between a scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in Caenorhabditis elegans
    • Using a yeast two-hybrid screen and functional genetic analysis, the authors find that the scaffolding protein, NAB-1, binds to the SAD-1 protein kinase via its PDZ domain. NAB-1 is expressed in neurons and co-localizes with SAD-1 at synapses. nab-1 mutants have defects in axon polarity, and nab-1 acts in the same genetic pathway as sad-1. However, nab-1 mutants have normal synapses. Thus, nab-1 mediates the function of sad-1 in axon polarity but not synapse formation in the D-type neurons.
    • Hung W., Hwang C., Po M.D., and Zhen M. Neuronal polarity is regulated by a direct interaction between a scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in Caenorhabditis elegans. Development 134 (2007) 237-249. Using a yeast two-hybrid screen and functional genetic analysis, the authors find that the scaffolding protein, NAB-1, binds to the SAD-1 protein kinase via its PDZ domain. NAB-1 is expressed in neurons and co-localizes with SAD-1 at synapses. nab-1 mutants have defects in axon polarity, and nab-1 acts in the same genetic pathway as sad-1. However, nab-1 mutants have normal synapses. Thus, nab-1 mediates the function of sad-1 in axon polarity but not synapse formation in the D-type neurons.
    • (2007) Development , vol.134 , pp. 237-249
    • Hung, W.1    Hwang, C.2    Po, M.D.3    Zhen, M.4
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    • Systematic analysis of genes required for synapse structure and function
    • The authors perform the first large-scale RNAi screen to identify molecules that regulate synapse function and formation. 12 molecules identified in the screen localize to synapses and regulate presynaptic formation. These include 11 novel regulators of synapse formation that fall into several broad categories including protein kinases, Ras GTPases, protein scaffolds, as well as known and putative regulators of endocytosis and ubiquitination-mediated protein trafficking.
    • Sieburth D., Ch'ng Q., Dybbs M., Tavazoie M., Kennedy S., Wang D., Dupuy D., Rual J.F., Hill D.E., Vidal M., et al. Systematic analysis of genes required for synapse structure and function. Nature 436 (2005) 510-517. The authors perform the first large-scale RNAi screen to identify molecules that regulate synapse function and formation. 12 molecules identified in the screen localize to synapses and regulate presynaptic formation. These include 11 novel regulators of synapse formation that fall into several broad categories including protein kinases, Ras GTPases, protein scaffolds, as well as known and putative regulators of endocytosis and ubiquitination-mediated protein trafficking.
    • (2005) Nature , vol.436 , pp. 510-517
    • Sieburth, D.1    Ch'ng, Q.2    Dybbs, M.3    Tavazoie, M.4    Kennedy, S.5    Wang, D.6    Dupuy, D.7    Rual, J.F.8    Hill, D.E.9    Vidal, M.10
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    • The requirement for Phr1 in CNS axon tract formation reveals the corticostriatal boundary as a choice point for cortical axons
    • The authors generate a conditional knockout of Phr1, the mammalian ortholog of the ubiquitin ligases highwire (in Drosophila) and rpm-1 (in C. elegans). They find that Phr1 plays a cell-autonomous role in sculpting motor nerve terminals, similar to its invertebrate homologs. Interestingly, the authors also find that Phr1 plays a non-cell-autonomous role in the formation of major CNS tracts, and that this role is not suppressed by the loss of function in the mammalian MAPKKK DLK (unlike other previously described highwire/rpm-1 functions, which are mediated by dlk-1).
    • Bloom A.J., Miller B.R., Sanes J.R., and DiAntonio A. The requirement for Phr1 in CNS axon tract formation reveals the corticostriatal boundary as a choice point for cortical axons. Genes Dev 21 (2007) 2593-2606. The authors generate a conditional knockout of Phr1, the mammalian ortholog of the ubiquitin ligases highwire (in Drosophila) and rpm-1 (in C. elegans). They find that Phr1 plays a cell-autonomous role in sculpting motor nerve terminals, similar to its invertebrate homologs. Interestingly, the authors also find that Phr1 plays a non-cell-autonomous role in the formation of major CNS tracts, and that this role is not suppressed by the loss of function in the mammalian MAPKKK DLK (unlike other previously described highwire/rpm-1 functions, which are mediated by dlk-1).
    • (2007) Genes Dev , vol.21 , pp. 2593-2606
    • Bloom, A.J.1    Miller, B.R.2    Sanes, J.R.3    DiAntonio, A.4
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    • The ubiquitin ligase Phr1 regulates axon outgrowth through modulation of microtubule dynamics
    • The authors perform a forward genetic screen for defects in neuronal pathfinding in mice, and identify the mutation Magellan in the ubiquitin ligase gene Phr1/highwire/rpm-1. Phr1 associates with microtubules in the axon shaft but is excluded from the growth cone. The authors find that Phr1 functions to stabilize microtubules within the axon and inhibit formation of growth cones. This effect is probably mediated by the orthologs of the DLK-1 signaling cascade, since inhibiting the activity of a downstream effector, p38MAPK, can suppress the Magellan phenotype.
    • Lewcock J.W., Genoud N., Lettieri K., and Pfaff S.L. The ubiquitin ligase Phr1 regulates axon outgrowth through modulation of microtubule dynamics. Neuron 56 (2007) 604-620. The authors perform a forward genetic screen for defects in neuronal pathfinding in mice, and identify the mutation Magellan in the ubiquitin ligase gene Phr1/highwire/rpm-1. Phr1 associates with microtubules in the axon shaft but is excluded from the growth cone. The authors find that Phr1 functions to stabilize microtubules within the axon and inhibit formation of growth cones. This effect is probably mediated by the orthologs of the DLK-1 signaling cascade, since inhibiting the activity of a downstream effector, p38MAPK, can suppress the Magellan phenotype.
    • (2007) Neuron , vol.56 , pp. 604-620
    • Lewcock, J.W.1    Genoud, N.2    Lettieri, K.3    Pfaff, S.L.4
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    • Disruption of Esrom and Ryk identifies the roof plate boundary as an intermediate target for commissure formation
    • Hendricks M., Mathuru A.S., Wang H., Silander O., Kee M.Z., and Jesuthasan S. Disruption of Esrom and Ryk identifies the roof plate boundary as an intermediate target for commissure formation. Mol Cell Neurosci 37 (2008) 271-283
    • (2008) Mol Cell Neurosci , vol.37 , pp. 271-283
    • Hendricks, M.1    Mathuru, A.S.2    Wang, H.3    Silander, O.4    Kee, M.Z.5    Jesuthasan, S.6


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.