Golgi Cisternae Pericentriolar Stack Reorganization

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Homo sapiens
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The pericentriolar stacks of Golgi cisternae undergo extensive fragmentation and reorganization in mitosis.

In mammalian cells, Golgi apparatus consists of stacked cisternae that are connected by tubules to form a ribbon-like structure in the perinuclear region, in vicinity of the centrosome. Reorganization of the Golgi apparatus during cell division allows both daughter cells to inherit this organelle, and may play additional roles in the organization of the mitotic spindle.

First changes in the structure of the Golgi apparatus likely start in G2 and are subtle, involving unlinking of the Golgi ribbon into separate stacks. These changes are required for the entry of mammalian cells into mitosis (Sutterlin et al. 2002). This initial unlinking of the Golgi ribbon depends on GRASP proteins and on CTBP1 (BARS) protein, which induces the cleavage of the tubular membranes connecting the stacks (Hidalgo Carcedo et al. 2004, Colanzi et al. 2007), but the exact mechanism is not known. Activation of MEK1/2 also contributes to unlinking of the Golgi ribbon in G2 (Feinstein and Linstedt 2007).

From prophase to metaphase, Golgi cisternae undergo extensive fragmentation that is a consequence of unstacking of Golgi cisternae and cessation of transport through Golgi. At least three mitotic kinases, CDK1, PLK1 and MEK1, regulate these changes. CDK1 in complex with cyclin B phosphorylates GOLGA2 (GM130) and GORASP1 (GRASP65), constituents of a cis-Golgi membrane complex (Lowe et al. 1998, Preisinger et al. 2005). Phosphorylation of GOLGA2 prevents binding of USO1 (p115), a protein localizing to the membrane of ER (endoplasmic reticulum) to Golgi transport vesicles and cis-Golgi, thereby impairing fusion of these vesicles with cis-Golgi cisternae and stopping ER to Golgi transport (Lowe et al. 1998, Seeman et al. 2000, Moyer et al. 2001). Phosphorylation of GORASP1 by CDK1 enables further phosphorylation of GORASP1 by PLK1 (Sutterlin et al. 2001, Preisinger et al. 2005). Phosphorylation of GORASP1 by CDK1 and PLK1 impairs stacking of Golgi cisternae by interfering with formation of GORASP1 trans-oligomers that would normally link the Golgi cisternae together (Wang et al. 2003, Wang et al. 2005, Sengupta and Linstedt 2010).

In the median Golgi, GORASP2 (GRASP55), a protein that forms a complex with BLFZ1 (Golgin-45) and RAB2A GTPase and contributes to cisternae stacking and Golgi trafficking (Short et al. 2001), is also phosphorylated in mitosis. Phosphorylation of GORASP2 by MEK1/2-activated MAPK1 (ERK2) and/or MAPK3-3 (ERK1b in human, Erk1c in rat) contributes to Golgi unlinking in G2 and fragmentation of Golgi cisternae in mitotic prophase (Acharya et al. 1998, Jesch et al. 2001, Colanzi et al. 2003, Shaul and Seger 2006, Duran et al. 2008, Feinstein and Linstedt 2007, Feinstein and Linstedt 2008, Xiang and Wang 2010).
Literature References
PubMed ID Title Journal Year
11408587 Mitotic phosphorylation of Golgi reassembly stacking protein 55 by mitogen-activated protein kinase ERK2

Linstedt, AD, Ahn, NG, Lewis, TS, Jesch, SA

Mol. Biol. Cell 2001
10679020 The role of the tethering proteins p115 and GM130 in transport through the Golgi apparatus in vivo

Seemann, J, Jokitalo, EJ, Warren, G

Mol. Biol. Cell 2000
18385516 The role of GRASP55 in Golgi fragmentation and entry of cells into mitosis

Bossard, C, Kinseth, M, Wu, CC, Zimmerman, T, Duran, JM, Yates, J, Malhotra, V, Polishchuk, R, Rose, DW

Mol. Biol. Cell 2008
12839990 A direct role for GRASP65 as a mitotically regulated Golgi stacking factor

Seemann, J, Warren, G, Wang, Y, Shorter, J, Pypaert, M

EMBO J. 2003
15576368 Mapping the functional domains of the Golgi stacking factor GRASP65

Satoh, A, Warren, G, Wang, Y

J. Biol. Chem. 2005
12015985 Fragmentation and dispersal of the pericentriolar Golgi complex is required for entry into mitosis in mammalian cells

Hsu, P, Sütterlin, C, Mallabiabarrena, A, Malhotra, V

Cell 2002
15232108 Mitotic Golgi partitioning is driven by the membrane-fissioning protein CtBP3/BARS

Colanzi, A, Bonazzi, M, Corda, D, Turacchio, G, Spanò, S, Luini, A, Hidalgo Carcedo, C

Science 2004
11739401 A GRASP55-rab2 effector complex linking Golgi structure to membrane traffic

Preisinger, C, Barr, FA, Kopajtich, R, Short, B, Byron, O, Körner, R

J. Cell Biol. 2001
20937827 Mitotic inhibition of GRASP65 organelle tethering involves Polo-like kinase 1 (PLK1) phosphorylation proximate to an internal PDZ ligand

Sengupta, D, Linstedt, AD

J. Biol. Chem. 2010
11285137 Rab1 interaction with a GM130 effector complex regulates COPII vesicle cis--Golgi tethering

Allan, BB, Balch, WE, Moyer, BD

Traffic 2001
16533948 ERK1c regulates Golgi fragmentation during mitosis

Shaul, YD, Seger, R

J. Cell Biol. 2006
20083603 GRASP55 and GRASP65 play complementary and essential roles in Golgi cisternal stacking

Xiang, Y, Wang, Y

J. Cell Biol. 2010
17431394 The Golgi mitotic checkpoint is controlled by BARS-dependent fission of the Golgi ribbon into separate stacks in G2

Colanzi, A, Bonazzi, M, Corda, D, Turacchio, G, Cericola, C, Luini, A, Persico, A, Hidalgo Carcedo, C

EMBO J. 2007
9753325 Cdc2 kinase directly phosphorylates the cis-Golgi matrix protein GM130 and is required for Golgi fragmentation in mitosis

Rahman, D, Rabouille, C, Watson, R, Jackman, M, Nakamura, N, Warren, G, Pappin, DJC, Jämsä, E, Lowe, M

Cell 1998
12695496 RAF1-activated MEK1 is found on the Golgi apparatus in late prophase and is required for Golgi complex fragmentation in mitosis

Colanzi, A, Sutterlin, C, Malhotra, V

J. Cell Biol. 2003
18434598 GRASP55 regulates Golgi ribbon formation

Linstedt, AD, Feinstein, TN

Mol. Biol. Cell 2008
17182854 Mitogen-activated protein kinase kinase 1-dependent Golgi unlinking occurs in G2 phase and promotes the G2/M cell cycle transition

Linstedt, AD, Feinstein, TN

Mol. Biol. Cell 2007
15678101 Plk1 docking to GRASP65 phosphorylated by Cdk1 suggests a mechanism for Golgi checkpoint signalling

Wind, M, Barr, FA, Korner, R, Kopajtich, R, Lehmann, WD, Preisinger, C

EMBO J 2005
9458043 Signaling via mitogen-activated protein kinase kinase (MEK1) is required for Golgi fragmentation during mitosis

Mallabiabarrena, A, Acharya, JK, Malhotra, V, Acharya, U

Cell 1998
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