Three-dimensional structure of the amino-terminal domain of syntaxin 6, a SNAP-25 C homolog

Misura, Kira M. S.; Bock, Jason B.; Gonzalez, Lino C.; Scheller, Richard H.; Weis, William I.

doi:10.1073/pnas.132274599

Cited by 49 publications

(48 citation statements)

References 33 publications

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“…Similarly, all Qa-SNAREs exhibit a very similar domain architecture, carrying an N-terminal three-helix bundle structure (Fernandez et al, 1998;Lerman et al, 2000;Misura et al, 2000;Munson et al, 2000;Dulubova et al, 2001). Interestingly, several of the Qb-and the Qc-SNAREs possess an N-terminal three-helix bundle as well (Antonin et al, 2002a;Misura et al, 2002;Fridmann-Sirkis et al, 2006). This hints at a common origin of all three main Q-SNARE groups from a prototypic Q-SNARE.…”

Section: Evolution Of the Snare Apparatus Is Linked To The Developmenmentioning

confidence: 96%

An Elaborate Classification of SNARE Proteins Sheds Light on the Conservation of the Eukaryotic Endomembrane System

Kloepper

Kienle

Fasshauer

2007

MBoC

229

286

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Proteins of the SNARE (soluble N-ethylmalemide-sensitive factor attachment protein receptor) family are essential for the fusion of transport vesicles with an acceptor membrane. Despite considerable sequence divergence, their mechanism of action is conserved: heterologous sets assemble into membrane-bridging SNARE complexes, in effect driving membrane fusion. Within the cell, distinct functional SNARE units are involved in different trafficking steps. These functional units are conserved across species and probably reflect the conservation of the particular transport step. Here, we have systematically analyzed SNARE sequences from 145 different species and have established a highly accurate classification for all SNARE proteins. Principally, all SNAREs split into four basic types, reflecting their position in the four-helix bundle complex. Among these four basic types, we established 20 SNARE subclasses that probably represent the original repertoire of a eukaryotic cenancestor. This repertoire has been modulated independently in different lines of organisms. Our data are in line with the notion that the ur-eukaryotic cell was already equipped with the various compartments found in contemporary cells. Possibly, the development of these compartments is closely intertwined with episodes of duplication and divergence of a prototypic SNARE unit. INTRODUCTIONThe elaborate endomembrane system of eukaryotes is thought to have evolved by invagination of the plasma membrane during perfection of a phagotrophic lifestyle. Subsequently, primitive endomembranes differentiated into the various spatially and functionally separated compartments found in contemporary eukaryotes (Roger, 1999;Cavalier-Smith, 2002). Material exchange is mediated by cargo-loaded vesicles that bud from the donor and eventually fuse with the acceptor compartment. This allows the cells to take up nutrients through the endocytic pathway. Conversely, newly synthesized proteins and lipids are transported within the cell through the exocytic pathway. As each organelle must maintain its identity, vesicular trafficking is tightly regulated (Bonifacino and Glick, 2004). Although some protists possess highly divergent compartments, it is becoming clear that the underlying molecular machineries involved in vesicular trafficking are highly conserved among all eukaryotes. Key players in the concluding step, the fusion of a vesicle with its acceptor membrane, are the so-called SNARE (soluble N-ethylmalemide-sensitive factor attachment protein receptor) proteins (reviewed in Hong, 2005;Jahn and Scheller, 2006). They form a family of small cytoplasmically orientated membrane-associated proteins that comprise a relatively simple domain architecture. Their characteristic is the so-called SNARE motif, an extended segment arranged in heptad repeats. In most SNAREs the motif is C-terminally connected to a single transmembrane domain by a short linker.As general mechanism it is thought that the SNAREs on the transport vesicle form a tight complex with the SNAREs in the ac...

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Section: Evolution Of the Snare Apparatus Is Linked To The Developmenmentioning

confidence: 96%

An Elaborate Classification of SNARE Proteins Sheds Light on the Conservation of the Eukaryotic Endomembrane System

Kloepper

Kienle

Fasshauer

2007

MBoC

229

286

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“…The N-terminal domains of Tlg2p, Vti1p, and the Tlg1p homolog syntaxin 6 have recently been shown to all possess a strong structural similarity to that of syntaxin, but none appears to form a closed conformation in vitro (Antonin et al, 2002;Dulubova et al, 2002;Misura et al, 2002). It may be that intramolecular SNARE interactions are not always readily detected in vitro, because the results of the liposome fusion work are most consistent with the model that an unidentified factor catalyzes SNARE assembly by displacing an inhibitory domain.…”

Section: Vps51 Is Required For the Binding Of Garp To The Tgn T-snarementioning

confidence: 99%

“…Recent studies have demonstrated that many nonsyntaxin SNAREs, including the Tlg1p homolog syntaxin 6, have a conserved, independently folded N-terminal domain that is structurally similar to that of syntaxin (Dulubova et al, 2001;Tochio et al, 2001;Misura et al, 2002). To identify which domain of Tlg1p is responsible for binding Vps51p, we expressed the entire soluble (cytosolic) por- Figure 5.…”

Section: Vps51p Is Required For the Binding Of Vps52/53/54 To The N-tmentioning

confidence: 99%

Vps51p Mediates the Association of the GARP (Vps52/53/54) Complex with the Late Golgi t-SNARE Tlg1p

Conibear

Cleck

Stevens

2003

MBoC

174

227

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Multisubunit tethering complexes may contribute to the specificity of membrane fusion events by linking transport vesicles to their target membrane in an initial recognition event that promotes SNARE assembly. However, the interactions that link tethering factors to the other components of the vesicle fusion machinery are still largely unknown. We have previously identified three subunits of a Golgi-localized complex (the Vps52/53/54 complex) that is required for retrograde transport to the late Golgi. This complex interacts with a Rab and a SNARE protein found at the late Golgi and is related to two other multisubunit tethering complexes: the COG complex and the exocyst. Here we show that the Vps52/53/54 complex has an additional subunit, Vps51p. All four members of this tetrameric GARP (Golgi-associated retrograde protein) complex are required for two distinct retrograde transport pathways, from both early and late endosomes, back to the TGN. vps51 mutants exhibit a distinct phenotype suggestive of a regulatory role. Indeed, we find that Vps51p mediates the interaction between Vps52/53/54 and the t-SNARE Tlg1p. The binding of this small, coiled-coil protein to the conserved N-terminal domain of the t-SNARE therefore provides a crucial link between components of the tethering and the fusion machinery.

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“…For example, caveolar endocytosis was dramatically reduced following inhibition of Stx6; however, this was not due to the direct participation of the SNARE to the process but upon the block of membrane microdomain delivery to the plasmalemma (Choudhury et al, 2006). Moreover, the SNARE motif of Stx6 appears structurally and functionally more homologous to the Qc motif of the SNAPs than to the Qa motif of other syntaxins (Bock et al, 2001;Misura et al, 2002). Therefore, a SNARE complex including both Stx6 and SNAP23 might be unlikely because it would be composed, together with the Qb motif of SNAP23 and the R motif of VAMP4, by two Qc and no Qa motifs.…”

Section: Journal Of Cell Science 121 (18)mentioning

confidence: 99%

The regulated exocytosis of enlargeosomes is mediated by a SNARE machinery that includes VAMP4

Cocucci

Racchetti

Rupnik

et al. 2008

Journal of Cell Science

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The mechanisms governing the fast, regulated exocytosis of enlargeosomes have been unknown, except for the participation of annexin-2 in a pre-fusion step. We investigated whether any SNAREs are involved. In PC12-27 cells, which are enlargeosome-rich, the expressed SNAREs exhibited various distributions (trans-Golgi network, scattered puncta, plasma membrane); however, only VAMP4 was colocalized in discrete puncta with the enlargeosome marker desmoyokin. The exocytosis of the organelle, revealed by capacitance increases and by surface appearance of desmoyokin, was largely inhibited by microinjection of anti-VAMP4, anti-syntaxin-6 and anti-SNAP23 antibodies, by incubation with botulinum toxin E, and by transfection of VAMP4 and syntaxin-6 siRNAs. Microinjection of the antibodies anti-VAMP7, anti-VAMP8 and anti-syntaxin-4, and transfection with the VAMP8 siRNA were ineffective. Inhibition of enlargeosome exocytosis by VAMP4 siRNA also occurred in a cell type that was competent for neurosecretion, SH-SY5Y. Moreover, in cells expressing a VAMP4-GFP construct, enlargeosome exocytosis and surface appearance of fluorescence occurred concomitantly, and many ensuing surface patches were co-labelled by GFP and desmoyokin. VAMP4, an R-SNARE that has never been shown to participate in regulated exocytoses, therefore appears to be harboured in the membrane of enlargeosomes and to be a member of the machinery mediating their regulated exocytosis. Syntaxin-6 and SNAP23 appear also to be needed for the process to occur; however, the mechanism of their participation, whether direct or indirect, remains undefined.

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Three-dimensional structure of the amino-terminal domain of syntaxin 6, a SNAP-25 C homolog

Cited by 49 publications

References 33 publications

An Elaborate Classification of SNARE Proteins Sheds Light on the Conservation of the Eukaryotic Endomembrane System

An Elaborate Classification of SNARE Proteins Sheds Light on the Conservation of the Eukaryotic Endomembrane System

Vps51p Mediates the Association of the GARP (Vps52/53/54) Complex with the Late Golgi t-SNARE Tlg1p

The regulated exocytosis of enlargeosomes is mediated by a SNARE machinery that includes VAMP4

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