GRASP65, a Protein Involved in the Stacking of Golgi Cisternae

Barr, Francis A.; Puype, Magda; Vandekerckhove, Joël; Warren, Graham

doi:10.1016/s0092-8674(00)80407-9

Cited by 400 publications

(517 citation statements)

References 27 publications

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“…GRASP55-T 222,225 D was also defective in oligomer formation, supporting a model in which the homotypic fusion underlying Golgi ribbon formation depends on membrane cross-bridging by GRASP55 transoligomers. This model for the function of mammalian GRASP proteins largely agrees with previous work on Golgi assembly (Barr et al, 1997;Shorter et al, 1999;Wang et al, 2003Wang et al, , 2005, but its relevance to other described functions for GRASP55 and GRASP65 remains to be determined. GRASP55 binds and may facilitate transport of the transmembrane growth factor ␣ (Kuo et al, 2000), and both GRASP proteins bind members of the p24 protein family, thereby inhibiting p24 recycling to the ER (Barr et al, 2001).…”

Section: Discussionsupporting

confidence: 85%

GRASP55 Regulates Golgi Ribbon Formation

Feinstein

Linstedt

2008

MBoC

143

196

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Recent work indicates that mitogen-activated protein kinase kinase (MEK)1 signaling at the G2/M cell cycle transition unlinks the contiguous mammalian Golgi apparatus and that this regulates cell cycle progression. Here, we sought to determine the role in this pathway of Golgi reassembly protein (GRASP)55, a Golgi-localized target of MEK/extracellular signal-regulated kinase (ERK) phosphorylation at mitosis. In support of the hypothesis that GRASP55 is inhibited in late G2 phase, causing unlinking of the Golgi ribbon, we found that HeLa cells depleted of GRASP55 show a fragmented Golgi similar to control cells arrested in G2 phase. In the absence of GRASP55, Golgi stack length is shortened but Golgi stacking, compartmentalization, and transport seem normal. Absence of GRASP55 was also sufficient to suppress the requirement for MEK1 in the G2/M transition, a requirement that we previously found depends on an intact Golgi ribbon. Furthermore, mimicking mitotic phosphorylation of GRASP55 by using aspartic acid substitutions is sufficient to unlink the Golgi apparatus in a gene replacement assay. Our results implicate MEK1/ERK regulation of GRASP55-mediated Golgi linking as a control point in cell cycle progression. INTRODUCTIONThe structural diversity of the Golgi apparatus among eukaryotes suggests two primary modes of organization. Cis-, medial-, and trans-Golgi cisternae, although unconnected in budding yeast, are typically present as membrane stacks. Whereas many cell types contain numerous scattered stacks positioned adjacent to endoplasmic reticulum (ER) exit sites, known as ministacks, mammalian cells and those from related metazoans exhibit a pericentrosomal Golgi in which ministacks are laterally linked into a ribbon. The in vivo requirements for Golgi stack formation remain unknown; however, recent work has begun to identify components necessary for linking cisternal stacks into a contiguous Golgi ribbon.Depletion of the golgin Golgi matrix protein 130 kDa (GM130), or its binding partner Golgi reassembly protein (GRASP)65, by using RNA interference (RNAi) specifically disrupts formation of the Golgi ribbon (Puthenveedu et al., 2006). GM130 seems to recruit GRASP65 to Golgi membranes because Golgi localization of GRASP65 is lost upon GM130 knockdown, whereas GM130 remains Golgi localized in the absence of GRASP65 (Sutterlin et al., 2005;Puthenveedu et al., 2006). A mechanism for Golgi ribbon formation by GRASP65 is suggested by the finding that two postsynaptic density 95/disc-large/zona occludens-like domains at the N terminus of GRASP65 form oligomers that, in the presence of cytosol, can cross-link beads (Wang et al., 2003(Wang et al., , 2005. Thus, the Golgi ribbon may be formed by GM130-dependent recruitment of GRASP65 to Golgi cisternal rims where GRASP65 transoligomer formation crossbridges adjacent cis-cisternae and possibly primes them for soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated membrane fusion (Puthenveedu et al., 2006).The lateral contacts that form the Gol...

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Section: Discussionsupporting

confidence: 85%

GRASP55 Regulates Golgi Ribbon Formation

Feinstein

Linstedt

2008

MBoC

143

196

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“…GRASP65 was first described by Barr, Warren and colleagues as a Golgi cisternal stacking factor using an in vitro Golgi reassembly assay. 49 However, RNAi studies have later shown that its main function may not be in cisternal stacking, [50][51][52] but in the formation and/or maintenance of the tubules connecting the stacks within the Golgi ribbon. 52 GRASP65 is a major mitotically-phosphorylated Golgi protein.…”

Section: The Golgi Mitotic Checkpoint Is Regulated By the Golgi Ribbomentioning

confidence: 99%

“…52 GRASP65 is a major mitotically-phosphorylated Golgi protein. [41][42]49 Detailed mapping by mass spectrometry has revealed 4 CDK1-cyclinB phosphorylation sites and two other potential mitotically-regulated phosphorylation sites by nonidentified kinases. 46 All these sites are located at the serine/proline-rich C-terminal portion.…”

Section: The Golgi Mitotic Checkpoint Is Regulated By the Golgi Ribbomentioning

confidence: 99%

Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint

Rabouille¹,

Kondylis²

2007

Cell Cycle

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Cell cycle checkpoints have been associated mostly with signaling mechanisms monitoring the genetic material for abnormalities and inaccuracy in partitioning, such as DNA lesions or failure in chromosome attachment to kinetochores. However, it becomes more evident that other checkpoints are turned on by cytoplasmic events, such as the cytoskeleton organization and the organelle structure. Here, we summarize recent evidence strongly suggesting that the integrity of the Golgi ribbon and more precisely the tubules interconnecting the Golgi stacks to form this ribbon, at late G 2 /early prophase, is linked to a Golgi-related G 2 /M checkpoint. A number of kinases phosphorylating a small subset of Golgi-localized proteins have been shown to promote the G 2 -specific Golgi ribbon unlinking, allowing the cell to enter mitosis. When these kinases are inactivated or when the substrates cannot be phosphorylated, Golgi unlinking is prevented and the cells are blocked or delayed in G 2 phase.

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“…This observation suggests a mechanism whereby the dispersion of vesicles and tubules into the cytoplasm is prevented. They act as if they were anchored on a template or the "zone of exclusion" (Mollenhauer and Morré, 1978;Rabouille et al, 1995b;Barr et al, 1997). The anchoring of vesicles is thought to be an essential part of the formation of Golgi cisternae.…”

Section: Golgi Stack Biogenesis In Vivomentioning

confidence: 99%

“…Syntaxin 5 was shown to interact with both fusion machineries . p115 (Rabouille et al, 1995a), Golgi matrix 130 (GM130) , GRASP65 (Barr et al, 1997), and GRASP55 were shown to be involved.…”

Section: Introductionmentioning

confidence: 98%

Biogenesis of Golgi Stacks in Imaginal Discs ofDrosophila melanogaster

Kondylis

Goulding

Dunne

et al. 2001

MBoC

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We provide a detailed description of Golgi stack biogenesis that takes place in vivo during one of the morphogenetic events in the lifespan of Drosophila melanogaster. In early third-instar larvae, small clusters consisting mostly of vesicles and tubules were present in epithelial imaginal disk cells. As larvae progressed through mid-and late-third instar, these larval clusters became larger but also increasingly formed cisternae, some of which were stacked. In white pupae, the typical Golgi stack was observed. We show that larval clusters are Golgi stack precursors by 1) localizing various Golgi-specific markers to the larval clusters by electron and immunofluorescence confocal microscopy, 2) driving this conversion in wild-type larvae incubated at 37°C for 2 h, and 3) showing that this conversion does not take place in an NSF1 mutant (comt 17). The biological significance of this conversion became clear when we found that the steroid hormone 20-hydroxyecdysone (ecdysone) is critically involved in this conversion. In its absence, Golgi stack biogenesis did not occur and the larval clusters remained unaltered. We showed that dGM130 and sec23p expression increases approximately three-and fivefold, respectively, when discs are exposed to ecdysone in vivo and in vitro. Taken together, these results suggest that we have developed an in vivo system to study the ecdysone-triggered Golgi stack biogenesis.

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GRASP65, a Protein Involved in the Stacking of Golgi Cisternae

Cited by 400 publications

References 27 publications

GRASP55 Regulates Golgi Ribbon Formation

GRASP55 Regulates Golgi Ribbon Formation

Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint

Biogenesis of Golgi Stacks in Imaginal Discs ofDrosophila melanogaster

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GRASP65, a Protein Involved in the Stacking of Golgi Cisternae

Cited by 400 publications

References 27 publications

GRASP55 Regulates Golgi Ribbon Formation

GRASP55 Regulates Golgi Ribbon Formation

Golgi Ribbon Unlinking: An Organelle-Based G2/M Checkpoint

Biogenesis of Golgi Stacks in Imaginal Discs ofDrosophila melanogaster

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Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint