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Reorganization of the Golgi complex in association with mitosis: Redistribution of mannosidase II to the endoplasmic reticulum and effects of brefeldin A
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Immunoelectron microscopy revealed that Golgi enzymes are redistributed into the ER in mitotic cells. This was the beginning of the controversy regarding the fate of the Golgi membranes during mitosis in mammalian cells.
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Thyberg J., Moskalewski S. Reorganization of the Golgi complex in association with mitosis: redistribution of mannosidase II to the endoplasmic reticulum and effects of brefeldin A. J. Submicrosc. Cytol. Pathol. 24:1992;495-508 Immunoelectron microscopy revealed that Golgi enzymes are redistributed into the ER in mitotic cells. This was the beginning of the controversy regarding the fate of the Golgi membranes during mitosis in mammalian cells.
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Golgi membranes are absorbed into and re-emerge from the ER during mitosis
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Live-imaging, photo bleaching revealed the presence of Golgi enzymes in the ER in mitotic cells. The photo-bleaching experiment is the strongest in this manuscript. It would be valuable to test the kinetics of fluorescence recovery of mitotic cells with cells containing vesiculated Golgi membranes. For example, treatment of cells with the drug ilimaquinone converts Golgi membranes into small vesicles. If Golgi membranes are fused with the ER, as argued by the authors, then there should be a difference in fluorescence recovery between IQ treated cells and mitotic cells.
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Zaal K.J., Smith C.L., Polishchuk R.S., Altan N., Cole N.B., Ellenberg J., Hirschberg K., Presley J.F., Roberts T.H., Siggia E.et al. Golgi membranes are absorbed into and re-emerge from the ER during mitosis. Cell. 99:1999;589-601 Live-imaging, photo bleaching revealed the presence of Golgi enzymes in the ER in mitotic cells. The photo-bleaching experiment is the strongest in this manuscript. It would be valuable to test the kinetics of fluorescence recovery of mitotic cells with cells containing vesiculated Golgi membranes. For example, treatment of cells with the drug ilimaquinone converts Golgi membranes into small vesicles. If Golgi membranes are fused with the ER, as argued by the authors, then there should be a difference in fluorescence recovery between IQ treated cells and mitotic cells.
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Zaal, K.J.1
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Shima D.T., Haldar K., Pepperkok R., Watson R., Warren G. Partitioning of the Golgi apparatus during mitosis in living HeLa cells. J. Cell Biol. 137:1997;1211-1228.
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Mitotic Golgi is in a dynamic equilibrium between clustered and free vesicles independent of the ER
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Mitotic cells were fractionated by ultracentrifugation. ER- and Golgi-specific markers were found in different fractions, suggesting that these two compartments remain separate during mitosis. It cannot be ruled out, however, that the cells used in these experiments were only those that contain Golgi membranes diffusely dispersed (prometaphase to early anaphase). Golgi membranes in the preceding mitotic stages (late prophase to early metaphase) are known to be separate from the ER and would definitely show Golgi and ER membranes in different fractions by the procedure used by the authors.
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Jesch S.A., Mehta A.J., Velliste M., Murphy R.F., Linstedt A.D. Mitotic Golgi is in a dynamic equilibrium between clustered and free vesicles independent of the ER. Traffic. 2:2001;873-884 Mitotic cells were fractionated by ultracentrifugation. ER- and Golgi-specific markers were found in different fractions, suggesting that these two compartments remain separate during mitosis. It cannot be ruled out, however, that the cells used in these experiments were only those that contain Golgi membranes diffusely dispersed (prometaphase to early anaphase). Golgi membranes in the preceding mitotic stages (late prophase to early metaphase) are known to be separate from the ER and would definitely show Golgi and ER membranes in different fractions by the procedure used by the authors.
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Prescott A.R., Farmaki T., Thomson C., James J., Paccaud J.P., Tang B.L., Hong W., Quinn M., Ponnambalam S., Lucocq J. Evidence for prebudding arrest of ER export in animal cell mitosis and its role in generating Golgi partitioning intermediates. Traffic. 2:2001;321-335.
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Prescott, A.R.1
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A specific activation of the mitogen-activated protein kinase kinase 1 (MEK1) is required for Golgi fragmentation during mitosis
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The authors report that the conformation of mitotically activated MEK1 is different from the interphase MEK1. Additionally, the mitotically activated form of MEK1 fragments Golgi membranes even when its ability to activate cytosolic ERKs is inhibited. This provides further support for the proposal that MEK1 is specifically activated during mitosis and interacts with a novel Golgi-associated target.
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Colanzi A., Deerinck T.J., Ellisman M.H., Malhotra V. A specific activation of the mitogen-activated protein kinase kinase 1 (MEK1) is required for Golgi fragmentation during mitosis. J. Cell Biol. 149:2000;331-339 The authors report that the conformation of mitotically activated MEK1 is different from the interphase MEK1. Additionally, the mitotically activated form of MEK1 fragments Golgi membranes even when its ability to activate cytosolic ERKs is inhibited. This provides further support for the proposal that MEK1 is specifically activated during mitosis and interacts with a novel Golgi-associated target.
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Takizawa P.A., Yucel J.K., Veit B., Faulkner D.J., Deerinck T., Soto G., Ellisman M., Malhotra V. Complete vesiculation of Golgi membranes and inhibition of protein transport by a novel sea sponge metabolite, ilimaquinone. Cell. 73:1993;1079-1090.
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Signaling via mitogen-activated protein kinase kinase (MEK1) is required for Golgi fragmentation during mitosis
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Mitotic Golgi fragmentation was reconstituted in permeabilized NRK cells. This semi-intact cell assay led to the identification of MEK1 kinase, a key component of the mitogen-activated protein kinase, signaling cascade, in the Golgi fragmentation process. Interestingly, cytosolic ERK1 and ERK2, the known MEK1 substrates, were not required for this reaction. A Golgi-bound ERK or an ERK-like protein was revealed by fluorescence microscopy.
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Acharya U., Mallabiabarrena A., Acharya J.K., Malhotra V. Signaling via mitogen-activated protein kinase kinase (MEK1) is required for Golgi fragmentation during mitosis. Cell. 92:1998;183-192 Mitotic Golgi fragmentation was reconstituted in permeabilized NRK cells. This semi-intact cell assay led to the identification of MEK1 kinase, a key component of the mitogen-activated protein kinase, signaling cascade, in the Golgi fragmentation process. Interestingly, cytosolic ERK1 and ERK2, the known MEK1 substrates, were not required for this reaction. A Golgi-bound ERK or an ERK-like protein was revealed by fluorescence microscopy.
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••], polo-kinase 1, a mitotic kinase with an important role in the maturation of centrosomes, was shown to be required for mitotic Golgi fragmentation.
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••], polo-kinase 1, a mitotic kinase with an important role in the maturation of centrosomes, was shown to be required for mitotic Golgi fragmentation.
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RAF-1 activated MEK1 is found on the Golgi apparatus in late prophase and is required for Golgi fragmentation during mitosis
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The authors report that mitotically activated MEK1 is localized to the Golgi membranes during late prophase. This localization coincides with the initiation of the Golgi fragmentation process. However, the mechanism by which mitotic MEK1 is bound to the Golgi in late prophase and its Golgi-associated targets are not known.
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Colanzi A., Suetterlin C., Malhotra V. RAF-1 activated MEK1 is found on the Golgi apparatus in late prophase and is required for Golgi fragmentation during mitosis. J. Cell Biol. 161:2003;27-32 The authors report that mitotically activated MEK1 is localized to the Golgi membranes during late prophase. This localization coincides with the initiation of the Golgi fragmentation process. However, the mechanism by which mitotic MEK1 is bound to the Golgi in late prophase and its Golgi-associated targets are not known.
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Tyrosine-phosphorylated extracellular signal-regulated kinase associates with the Golgi complex during G2/M phase of the cell cycle: Evidence for regulation of Golgi structure
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Cha H., Shapiro P. Tyrosine-phosphorylated extracellular signal-regulated kinase associates with the Golgi complex during G2/M phase of the cell cycle: evidence for regulation of Golgi structure. J. Cell Biol. 153:2001;1355-1367.
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Jesch S.A., Lewis T.S., Ahn N.G., Linstedt A.D. Mitotic phosphorylation of Golgi reassembly stacking protein 55 by mitogen-activated protein kinase ERK2. Mol. Biol. Cell. 12:2001;1811-1817.
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Shorter J., Watson R., Giannakou M.E., Clarke M., Warren G., Barr F.A. GRASP55, a second mammalian GRASP protein involved in the stacking of Golgi cisternae in a cell-free system. EMBO J. 18:1999;4949-4960.
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The coiled-coil membrane protein golgin-84 is a novel Rab effector required for Golgi ribbon formation
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The Golgi-associated protein golgin-84 is shown to be required for linking stacks of Golgi cisternae in the pericentriolar region. Loss of golgin-84 resulted in disassembly of the Golgi apparatus into stacks, which were found dispersed throughout the cell. Golgin-84 is phosphorylated in mitotic cells; however, the significance of this phosphorylation in mitotic Golgi dynamics is not yet known.
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Diao A., Rahman D., Pappin D.J., Lucocq J., Lowe M. The coiled-coil membrane protein golgin-84 is a novel Rab effector required for Golgi ribbon formation. J. Cell Biol. 160:2003;201-212 The Golgi-associated protein golgin-84 is shown to be required for linking stacks of Golgi cisternae in the pericentriolar region. Loss of golgin-84 resulted in disassembly of the Golgi apparatus into stacks, which were found dispersed throughout the cell. Golgin-84 is phosphorylated in mitotic cells; however, the significance of this phosphorylation in mitotic Golgi dynamics is not yet known.
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Evidence that Golgi structure depends on a p115 activity that is independent of the vesicle tether components giantin and GM130
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The authors report that removal of GM130 from cells does not affect the overall organization of the Golgi apparatus. This finding challenges the role of GM130 as a key regulator of the organization of the Golgi apparatus.
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Puthenveedu M.A., Linstedt A.D. Evidence that Golgi structure depends on a p115 activity that is independent of the vesicle tether components giantin and GM130. J. Cell Biol. 155:2001;227-238 The authors report that removal of GM130 from cells does not affect the overall organization of the Golgi apparatus. This finding challenges the role of GM130 as a key regulator of the organization of the Golgi apparatus.
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The authors used a cell-free assay to show that fragmentation of the Golgi membranes by mitotic cytosol is through a COP1-dependent process. However, it is not known whether inhibiting COP1 activity in intact cells affects Golgi fragmentation during mitosis.
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Misteli T., Warren G. COP-coated vesicles are involved in the mitotic fragmentation of Golgi stacks in a cell-free system. J. Cell Biol. 125:1994;269-282 The authors used a cell-free assay to show that fragmentation of the Golgi membranes by mitotic cytosol is through a COP1-dependent process. However, it is not known whether inhibiting COP1 activity in intact cells affects Golgi fragmentation during mitosis.
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Cdc2 kinase directly phosphorylates the cis-Golgi matrix protein GM130 and is required for Golgi fragmentation in mitosis
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An in vitro assay that reconstitutes fragmentation of the isolated Golgi membrane into smaller elements upon incubation with mitotic cytosol was found to be cdc2 kinase-dependent. The Golgi associated protein GM130 is phosphorylated by cdc2 kinase. However, the significance of cdc2 kinase dependent phosphorylation of GM130 in mitosis specific Golgi dynamics is not known.
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Lowe M., Rabouille C., Nakamura N., Watson R., Jackman M., Jamsa E., Rahman D., Pappin D.J., Warren G. Cdc2 kinase directly phosphorylates the cis-Golgi matrix protein GM130 and is required for Golgi fragmentation in mitosis. Cell. 94:1998;783-793 An in vitro assay that reconstitutes fragmentation of the isolated Golgi membrane into smaller elements upon incubation with mitotic cytosol was found to be cdc2 kinase-dependent. The Golgi associated protein GM130 is phosphorylated by cdc2 kinase. However, the significance of cdc2 kinase dependent phosphorylation of GM130 in mitosis specific Golgi dynamics is not known.
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Lowe, M.1
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Seemann J., Jokitalo E.J., Warren G. The role of the tethering proteins p115 and GM130 in transport through the Golgi apparatus in vivo. Mol. Biol. Cell. 11:2000;635-645.
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Mitotic partitioning of endosomes and lysosomes
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In this paper, the authors show that endosomes and lysosomes remain intact during mitosis in mammalian cells. It is known that endocytosis is blocked during mitosis. A block in arrival of proteins into the endosomal pathway does not perturb the organization of the endosomes during mitosis. We use this information to raise an issue that imbalance of protein transport from ER to Golgi might not be the (only) reason for extensive Golgi fragmentation in mitosis.
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Bergeland T., Widerberg J., Bakke O., Nordeng T.W. Mitotic partitioning of endosomes and lysosomes. Curr. Biol. 11:2001;644-651 In this paper, the authors show that endosomes and lysosomes remain intact during mitosis in mammalian cells. It is known that endocytosis is blocked during mitosis. A block in arrival of proteins into the endosomal pathway does not perturb the organization of the endosomes during mitosis. We use this information to raise an issue that imbalance of protein transport from ER to Golgi might not be the (only) reason for extensive Golgi fragmentation in mitosis.
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Fragmentation and dispersal of the pericentriolar Golgi complex is required for entry into mitosis in mammalian cells
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The authors report that inhibiting fragmentation of pericentriolar Golgi apparatus prevents entry into mitosis. It is suggested that position of Golgi membranes acts as a sensor for regulating entry into mitosis. When fragmentation is inhibited, cells activate a machinery that inhibits progression into mitosis.
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Sutterlin C., Hsu P., Mallabiabarrena A., Malhotra V. Fragmentation and dispersal of the pericentriolar Golgi complex is required for entry into mitosis in mammalian cells. Cell. 109:2002;359-369 The authors report that inhibiting fragmentation of pericentriolar Golgi apparatus prevents entry into mitosis. It is suggested that position of Golgi membranes acts as a sensor for regulating entry into mitosis. When fragmentation is inhibited, cells activate a machinery that inhibits progression into mitosis.
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