A Role for Giantin in Docking COPI Vesicles to Golgi Membranes

Sönnichsen, Birte; Lowe, Martin; Levine, Tim P.; Jämsä, Eija; Dirac-Svejstrup, Barbara; Warren, Graham

doi:10.1083/jcb.140.5.1013

Cited by 273 publications

(265 citation statements)

References 40 publications

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“…This would be an attractive hypothesis, because it has been suggested that tethering may be linked to SNARE complex formation (64). However, amisyn is much smaller than the known tethering proteins like Uso1p (65), sec34p/sec35p (66), giantin (67,68), GM130 (69,70), and EEA1 (71). Thus, if amisyn were a tethering factor it would either tether membranes more closely than the above factors or be a component of a larger complex.…”

Section: Amisyn Coil Domain Inhibits the Rescue Of Exocytosis By Snapmentioning

confidence: 99%

Amisyn, a Novel Syntaxin-binding Protein That May Regulate SNARE Complex Assembly

Scales

Hesser

Masuda

et al. 2002

Journal of Biological Chemistry

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The regulation of SNARE complex assembly likely plays an important role in governing the specificity as well as the timing of membrane fusion. Here we identify a novel brain-enriched protein, amisyn, with a tomosynand VAMP-like coiled-coil-forming domain that binds specifically to syntaxin 1a and syntaxin 4 both in vitro and in vivo, as assessed by co-immunoprecipitation from rat brain. Amisyn is mostly cytosolic, but a fraction cosediments with membranes. The amisyn coil domain can form SNARE complexes of greater thermostability than can VAMP2 with syntaxin 1a and SNAP-25 in vitro, but it lacks a transmembrane anchor and so cannot act as a v-SNARE in this complex. The amisyn coil domain prevents the SNAP-25 C-terminally mediated rescue of botulinum neurotoxin E inhibition of norepinephrine exocytosis in permeabilized PC12 cells to a greater extent than it prevents the regular exocytosis of these vesicles. We propose that amisyn forms nonfusogenic complexes with syntaxin 1a and SNAP-25, holding them in a conformation ready for VAMP2 to replace it to mediate the membrane fusion event, thereby contributing to the regulation of SNARE complex formation.The exocytosis of synaptic and dense core vesicles with the plasma membrane in neurons and neuroendocrine cells requires proteins of the SNARE 1 families. The vesicle-associated membrane protein, VAMP2, a v-or R-SNARE, forms a specific SNARE complex with the target membrane-associated t-or Q-SNAREs syntaxin 1 and SNAP-25, whose parallel orientation brings the two membranes in close enough proximity to fuse (1, 2). Structurally the SNARE complex is a four-helix bundle comprised of one coiled-coil-forming domain from each of syntaxin and VAMP and two from 4). The center of the bundle is made up of 15 hydrophobic layers from the "a" and "d" positions of the heptad repeats of these coiled-coilforming domains, whereas the central "ionic" layer is highly conserved and polar in nature, containing a glutamine residue in the three t-SNAREs and an arginine in the v-SNARE (3), hence the classification of v-and t-SNAREs as R-and QSNAREs, respectively (5). The parallel orientation and high stability of the SNARE bundle led to the proposal that its formation drives the mixing of the membrane bilayers by zippering up through the transmembrane domains of syntaxin and VAMP (1, 2), and there is some evidence to support this (6 -9). After the fusion event, the SNAREs are in a cis-complex in the same membrane and must be dissociated by the action of the ATPase NSF and ␣-SNAP, so that SNAREs can be regenerated for the next round of fusion (10 -13).In addition to mediating the fusion event, the SNARE proteins have also been implicated in the specificity of membrane fusion, the SNARE hypothesis stating that a particular v-SNARE on a transport vesicle should only form a specific complex with its cognate t-SNARE on the correct target membrane, thereby ensuring that the vesicles only fuse with the right compartment (14). Although this hypothesis was cast into doubt by the finding that soluble ...

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Section: Amisyn Coil Domain Inhibits the Rescue Of Exocytosis By Snapmentioning

confidence: 99%

Amisyn, a Novel Syntaxin-binding Protein That May Regulate SNARE Complex Assembly

Scales

Hesser

Masuda

et al. 2002

Journal of Biological Chemistry

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“…However, COPI vesicles at every level are tethered to cisternae throughout the stack by flexible ''strings''-tethers that are long enough to permit vesicles to reach the adjoining cisternae on either side-effectively restraining transfers to the nearest neighbors in the stack (32,35). One system of strings, located at the cis face of the stack, has been well-characterized.…”

Section: Gos 28 Resides In the Same Copi-coated Buds And Vesicles Asmentioning

confidence: 99%

Anterograde flow of cargo across the Golgi stack potentially mediated via bidirectional “percolating” COPI vesicles

Orci

Ravazzola

Volchuk

et al. 2000

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

103

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How do secretory proteins and other cargo targeted to post-Golgi locations traverse the Golgi stack? We report immunoelectron microscopy experiments establishing that a Golgi-restricted SNARE, GOS 28, is present in the same population of COPI vesicles as anterograde cargo marked by vesicular stomatitis virus glycoprotein, but is excluded from the COPI vesicles containing retrograde-targeted cargo (marked by KDEL receptor). We also report that GOS 28 and its partnering t-SNARE heavy chain, syntaxin 5, reside together in every cisterna of the stack. Taken together, these data raise the possibility that the anterograde cargo-laden COPI vesicles, retained locally by means of tethers, are inherently capable of fusing with neighboring cisternae on either side. If so, quanta of exported proteins would transit the stack in GOS 28 -COPI vesicles via a bidirectional random walk, entering at the cis face and leaving at the trans face and percolating up and down the stack in between. Percolating vesicles carrying both post-Golgi cargo and Golgi residents up and down the stack would reconcile disparate observations on Golgi transport in cells and in cell-free systems.

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“…Tomosyn and p115 are of similar size and importantly contain a coiled-coil domain at their carboxyl termini that resembles the SNARE motif (66,67). p115 is thought to act as a tethering molecule by first linking Giantin on COP1-coated transport vesicles with the Golgi protein GM130 and subsequently promoting SNARE complex assembly on the target membrane (67,68). This role is consistent with the observation that expression of full-length Tomosyn was required to inhibit exocytosis, in vivo, and might indicate a separate but necessary role for the conserved aminoterminal domain of Tomosyn (18).…”

Section: Fig 7 Munc18c and B-tomosyn Binding To Syntaxin4 Is Not Mumentioning

confidence: 99%

Tomosyn Interacts with the t-SNAREs Syntaxin4 and SNAP23 and Plays a Role in Insulin-stimulated GLUT4 Translocation

Widberg

Bryant²,

Girotti³

et al. 2003

Journal of Biological Chemistry

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The Sec1p-like/Munc18 (SM) protein Munc18a binds to the neuronal t-SNARE Syntaxin1A and inhibits SNARE complex assembly. Tomosyn, a cytosolic Syntaxin1A-binding protein, is thought to regulate the interaction between Syntaxin1A and Munc18a, thus acting as a positive regulator of SNARE assembly. In the present study we have investigated the interaction between b-Tomosyn and the adipocyte SNARE complex involving Syntaxin4/SNAP23/VAMP-2 and the SM protein Munc18c, in vitro, and the potential involvement of Tomosyn in regulating the translocation of GLUT4 containing vesicles, in vivo. Tomosyn formed a high affinity ternary complex with Syntaxin4 and SNAP23 that was competitively inhibited by VAMP-2. Using a yeast two-hybrid assay we demonstrate that the VAMP-2-like domain in Tomosyn facilitates the interaction with Syntaxin4. Overexpression of Tomosyn in 3T3-L1 adipocytes inhibited the translocation of green fluorescent protein-GLUT4 to the plasma membrane. The SM protein Munc18c was shown to interact with the Syntaxin4 monomer, Syntaxin4 containing SNARE complexes, and the Syntaxin4/Tomosyn complex. These data suggest that Tomosyn and Munc18c operate at a similar stage of the Syntaxin4 SNARE assembly cycle, which likely primes Syntaxin4 for entry into the ternary SNARE complex.

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A Role for Giantin in Docking COPI Vesicles to Golgi Membranes

Cited by 273 publications

References 40 publications

Amisyn, a Novel Syntaxin-binding Protein That May Regulate SNARE Complex Assembly

Amisyn, a Novel Syntaxin-binding Protein That May Regulate SNARE Complex Assembly

Anterograde flow of cargo across the Golgi stack potentially mediated via bidirectional “percolating” COPI vesicles

Tomosyn Interacts with the t-SNAREs Syntaxin4 and SNAP23 and Plays a Role in Insulin-stimulated GLUT4 Translocation

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