Direct interaction between the COG complex and the SM protein, Sly1, is required for Golgi SNARE pairing

Laufman, Orly; Kedan, Amir; Hong, Wanjin; Lev, Sima

doi:10.1038/emboj.2009.168

Cited by 90 publications

(136 citation statements)

References 68 publications

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“…Consistent with this view, we previously showed that the MTC Conserved Oligomeric Golgi (COG) positively regulates the assembly of Syntaxin5 (Stx5)-GS28-Ykt6-GS15 and Stx6-Stx16-Vti1a-VAMP4 SNARE complexes (Laufman et al, 2011;Laufman et al, 2009). These Golgi SNARE complexes and their corresponding SM (Sec1/Munc18) proteins Sly1 and Vps45, regulate intra-Golgi and endosome-to-TGN retrograde transport, respectively (Li et al, 2005;Mallard et al, 2002;Rahajeng et al, 2010;Xu et al, 2002).…”

Section: Introductionmentioning

confidence: 53%

“…These Golgi SNARE complexes and their corresponding SM (Sec1/Munc18) proteins Sly1 and Vps45, regulate intra-Golgi and endosome-to-TGN retrograde transport, respectively (Li et al, 2005;Mallard et al, 2002;Rahajeng et al, 2010;Xu et al, 2002). Although, the mechanisms by which COG regulates the assembly of these SNARE complexes have not been fully resolved, our previous studies suggest that the direct interactions between the Cog4 subunit of the complex, Sly1, and Stx5, and between the Cog6 subunit and Stx6, are essential for SNARE complex assembly in mammalian cells (Laufman et al, 2011;Laufman et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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The COG complex interacts with multiple Golgi SNAREs and enhances fusogenic SNARE complexes assembly

Laufman

Hong

Lev

2013

Journal of Cell Science

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SummaryMultisubunit tethering complexes (MTCs) positively regulate vesicular fusion by as yet unclear mechanism. In this study we provide evidence that the MTC COG enhances the assembly of fusogenic Golgi SNARE complexes and concomitantly prevents nonfusogenic tSNARE interactions. This capability is possibly mediated by multiple direct interactions of COG subunits and specific Golgi SNAREs and SM (Sec1/Munc18) proteins. By using a systematic co-immunoprecipitation analysis, we identified seven new interactions between the COG subunits and components of the Golgi fusion machinery in mammalian cells. Our studies suggest that these multivalent interactions are critical for the assembly of fusogenic SNARE complexes on the Golgi apparatus and consequently for facilitating endosome-to-trans-Golgi network (TGN) and intra-Golgi retrograde transport, and also for coordinating these transport routes.

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Section: Introductionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

The COG complex interacts with multiple Golgi SNAREs and enhances fusogenic SNARE complexes assembly

Laufman

Hong

Lev

2013

Journal of Cell Science

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“…However, the Sec1/Munc18 protein for HOPS, Vps33, is a stoichiometric member of the HOPS complex, whereas the exocyst binds transiently to its Sec1/Munc18 protein, Sec1, through Sec6 (73,74). Similarly, the COG complex, which is structurally related to exocysts, binds both the Sec1/Munc18 proteins Sly1 and Vps45 through its Cog4 subunit (75,76). These similar protein-protein interactions suggest that additional interactions and roles may be conserved across trafficking pathways and across species.…”

Section: Discussionmentioning

confidence: 99%

The Exocyst Subunit Sec6 Interacts with Assembled Exocytic SNARE Complexes

Dubuke

Maniatis

Shaffer

et al. 2015

Journal of Biological Chemistry

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Background: Sec6 has been reported to inhibit SNARE complex assembly, in contrast to other tethering complexes. Results: Sec6 does not inhibit SNARE assembly. Rather, it binds assembled SNARE complexes. Disrupting this interaction results in growth defects in yeast. Conclusion: This interaction is important for a functional exocytic pathway. Significance: The exocyst is likely to have mechanisms of SNARE regulation comparable with other multisubunit tethering complexes.

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“…This region might, for example, interact directly with SNARE or SM proteins. It is intriguing in this regard that the region of lobe A where its four subunits interact has been shown to bind the SNARE protein Syntaxin-5 and the SM protein Sly1 (21,44,45). SNARE proteins assemble by forming membrane-bridging α-helical coiled-coil bundles, whereas SM proteins interact with and/or modulate formation of these bundles (46).…”

Section: Discussionmentioning

confidence: 99%

Cog5–Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex

Pokrovskaya

Climer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The conserved oligomeric Golgi (COG) complex is required, along with SNARE and Sec1/Munc18 (SM) proteins, for vesicle docking and fusion at the Golgi. COG, like other multisubunit tethering complexes (MTCs), is thought to function as a scaffold and/or chaperone to direct the assembly of productive SNARE complexes at the sites of membrane fusion. Reflecting this essential role, mutations in the COG complex can cause congenital disorders of glycosylation. A deeper understanding of COG function and dysfunction will likely depend on elucidating its molecular structure. Despite some progress toward this goal, including EM studies of COG lobe A (subunits 1-4) and higher-resolution structures of portions of Cog2 and Cog4, the structures of COG's eight subunits and the principles governing their assembly are mostly unknown. Here, we report the crystal structure of a complex between two lobe B subunits, Cog5 and Cog7. The structure reveals that Cog5 is a member of the complexes associated with tethering containing helical rods (CATCHR) fold family, with homology to subunits of other MTCs including the Dsl1, exocyst, and Golgi-associated retrograde protein (GARP) complexes. The Cog5-Cog7 interaction is analyzed in relation to the Dsl1 complex, the only other CATCHR-family MTC for which subunit interactions have been characterized in detail. Biochemical and functional studies validate the physiological relevance of the observed Cog5-Cog7 interface, indicate that it is conserved from yeast to humans, and demonstrate that its disruption in human cells causes defects in trafficking and glycosylation.I n eukaryotes, the transport of proteins and lipids among intracellular compartments is mediated by vesicular and tubular carriers under the direction of an elaborate protein machinery (1). Among the most complex and least well-characterized components of this machinery are the multisubunit tethering complexes (MTCs) (2). MTCs are thought to mediate the initial attachment (or tethering) between a trafficking vesicle and its target membrane through a constellation of interactions (3, 4). These may include binding of the MTC to activated Rab GTPases, coiled-coil proteins such as Golgins, vesicle coat proteins, SNAREs, Sec1/ Munc18 (SM) proteins, and/or membrane lipids. Elucidating the 3D structures of MTCs represents an important step toward a better understanding of their molecular functions.Four of the known MTCs-termed complexes associated with tethering containing helical rods (CATCHR) or quatrefoil complexes (2, 5)-contain subunits whose shared 3D structure implies a single evolutionary progenitor (6-16). These CATCHR-family MTCs include the Dsl1, Golgi-associated retrograde protein (GARP), exocyst, and conserved oligomeric Golgi (COG) complexes, and they contain three, four, eight, and eight subunits, respectively. Although X-ray or NMR structures have been reported for 14 of these 23 subunits, only one of the structures contains the full-length polypeptide (14). Perhaps more critically, only two subunit interactions-both wit...

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Direct interaction between the COG complex and the SM protein, Sly1, is required for Golgi SNARE pairing

Cited by 90 publications

References 68 publications

The COG complex interacts with multiple Golgi SNAREs and enhances fusogenic SNARE complexes assembly

The COG complex interacts with multiple Golgi SNAREs and enhances fusogenic SNARE complexes assembly

The Exocyst Subunit Sec6 Interacts with Assembled Exocytic SNARE Complexes

Cog5–Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex

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