The Golgi-Associated Protein GRASP Is Required for Unconventional Protein Secretion during Development

Kinseth, Matthew A.; Anjard, Christophe; Fuller, Danny; Guizzunti, Gianni; Loomis, William F.; Malhotra, Vivek

doi:10.1016/j.cell.2007.06.029

Cited by 225 publications

(283 citation statements)

References 45 publications

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“…Secretion of AcbA from these vesicles in response to GABA is dependent on the Golgi apparatus-associated protein GRASP (24). In contrast, secretion of the SDF-1 precursor does not depend on GRASP and is likely to exit via the conventional pathway (24). However, secretion of both precursors is dependent on the general membrane-trafficking factor NSF, indicating that vesicular fusion is a step in both pathways (reference 12 and unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…It appears to be packaged into vesicles derived from the autophagy pathway that become docked at the surface before release (12). Secretion of AcbA from these vesicles in response to GABA is dependent on the Golgi apparatus-associated protein GRASP (24). In contrast, secretion of the SDF-1 precursor does not depend on GRASP and is likely to exit via the conventional pathway (24).…”

Section: Discussionmentioning

confidence: 99%

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The Polyketide MPBD Initiates the SDF-1 Signaling Cascade That Coordinates Terminal Differentiation in Dictyostelium

Anjard

Loomis

2011

Eukaryot Cell

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Dictyostelium uses a wide array of chemical signals to coordinate differentiation as it switches from a unicellular to a multicellular organism. MPBD, the product of the polyketide synthase encoded by stlA, regulates stalk and spore differentiation by rapidly stimulating the release of the phosphopeptide SDF-1. By analyzing specific mutants affected in MPBD or SDF-1 production, we delineated a signal transduction cascade through the membrane receptor CrlA coupled to G␣1, leading to the inhibition of GskA so that the precursor of SDF-1 is released. It is then processed by the extracellular protease of TagB on prestalk cells. SDF-1 apparently acts through the adenylyl cyclase ACG to activate the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and trigger the production of more SDF-1. This signaling cascade shows similarities to the SDF-2 signaling pathway, which acts later to induce rapid spore encapsulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Polyketide MPBD Initiates the SDF-1 Signaling Cascade That Coordinates Terminal Differentiation in Dictyostelium

Anjard

Loomis

2011

Eukaryot Cell

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“…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). The GRASP homologues in Dictyostelium and Drosophila melanogaster, both of which organisms have one rather than two GRASP proteins, do not organize the nonlinked Golgi but rather contribute to unconventional secretion (Kinseth et al, 2007;Schotman et al, 2008), suggesting that linking of Golgi cisternae may be a later step in the evolutionary development of these proteins. Whether these selective transport functions of the GRASP protein constitute an inseparable part of its structural function, e.g., in membrane tethering, or whether selective transport represents a second and distinct function remains a compelling and unanswered question.…”

Section: Discussionmentioning

confidence: 99%

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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“…Autophagy-related proteins (ATGs) have been genetically implicated in the unconventional secretion of the acyl-CoA-binding protein Acb1 in yeast (AcbA in Dictyostelium discoideum), and inflammatory mediators such as interleukin-1β (IL-1β) and IL-18, the high mobility group protein B1 (HMGB1) and the integral membrane protein ΔF508 CFTR (cystic fibrosis transmembrane conductance regulator) in mammalian cells [127][128][129][130][131] . The unconventional secretion of these proteins is also dependent on Golgi membrane-binding proteins of the GRASP family in both yeast and mammals 129,130,132 .…”

Section: Box 2 | Autophagy and Secretionmentioning

confidence: 99%