A rab protein is required for the assembly of SNARE complexes in the docking of transport vesicles

Søgaard, Morten; Tani, Kazuhide; Ye, R.Ruby; Geromanos, Scott; Tempst, Paul; Kirchhausen, Tomas; Rothman, James E.; Söllner, Thomas H.

doi:10.1016/0092-8674(94)90270-4

Cited by 486 publications

(445 citation statements)

References 55 publications

Supporting

Mentioning

410

Contrasting

Unclassified

Order By: Relevance

“…In particular, our findings that reduced SNAP function results in elevated SNARE complex levels and reduced neurotransmitter release are consistent with the proposed biochemical role of SNAP in SNARE complex disassembly and secretion. Although the effect of reduced SNAP dosage on SNARE complex abundance in Drosophila conflicts with previous work in yeast (Sogaard et al, 1994), our results are consistent with those observed in Drosophila and yeast NSF mutants (Sogaard et al, 1994;Littleton et al, 1998;Tolar and Pallanck, 1998;Mohtashami et al, 2001). Thus, our results support previous biochemical studies indicating that these proteins collaborate to disassemble SNARE complexes but do not support studies in yeast suggesting that SNAP functions to stabilize SNARE complexes.…”

Section: Discussionsupporting

confidence: 34%

“…These observations are consistent with expectations from in vitro studies of NSF function and strongly support the involvement of NSF in SNARE complex disassembly. In contrast, SNARE complex abundance in yeast is correlated with SNAP activity, thus challenging the proposed role of this factor in SNARE complex disassembly (Sogaard et al, 1994;Wang et al, 2000). Although increased NSF activity does not detectably affect secretion (Golby et al, 2001), studies in yeast have shown that increased SNAP activity inhibits membrane fusion, and this inhibition can be overcome by a coordinate increase in NSF activity (Wang et al, 2000).…”

Section: Introductionmentioning

confidence: 97%

“…For example, studies in Drosophila and yeast have shown that SNARE complex abundance in these organisms is inversely correlated with NSF activity (Sogaard et al, 1994;Littleton et al, 1998;Tolar and Pallanck, 1998;Mohtashami et al, 2001). These observations are consistent with expectations from in vitro studies of NSF function and strongly support the involvement of NSF in SNARE complex disassembly.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic Analysis of SolubleN-Ethylmaleimide-Sensitive Factor Attachment Protein Function inDrosophilaReveals Positive and Negative Secretory Roles

Babcock¹,

Macleod²,

Leither³

et al. 2004

J. Neurosci.

View full text Add to dashboard Cite

The N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein (SNAP) are cytosolic factors that promote vesicle fusion with a target membrane in both the constitutive and regulated secretory pathways. NSF and SNAP are thought to function by catalyzing the disassembly of a SNAP receptor (SNARE) complex consisting of membrane proteins of the secretory vesicle and target membrane. Although studies of NSF function have provided strong support for this model, the precise biochemical role of SNAP remains controversial. To further explore the function of SNAP, we have used mutational and transgenic approaches in Drosophila to investigate the effect of altered SNAP dosage on neurotransmitter release and SNARE complex metabolism. Our results indicate that reduced SNAP activity results in diminished neurotransmitter release and accumulation of a neural SNARE complex. Increased SNAP dosage results in defective synapse formation and a variety of tissue morphological defects without detectably altering the abundance of neural SNARE complexes. The SNAP overexpression phenotypes are enhanced by mutations in other secretory components and are at least partially overcome by co-overexpression of NSF, suggesting that these phenotypes derive from a specific perturbation of the secretory pathway. Our results indicate that SNAP promotes neurotransmitter release and SNARE complex disassembly but inhibits secretion when present at high abundance relative to NSF.

show abstract

Section: Discussionsupporting

confidence: 34%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Analysis of SolubleN-Ethylmaleimide-Sensitive Factor Attachment Protein Function inDrosophilaReveals Positive and Negative Secretory Roles

Babcock¹,

Macleod²,

Leither³

et al. 2004

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In addition, Vti1p interacts both genetically and physically with Ykt6p (Lupashin et al, 1997). The v-SNARE Ykt6p is also found in a complex with Sed5p (Sogaard et al, 1994). Therefore, it is possible that Vti1p requires the presence of both Sft1p and Ykt6p for functional interaction with Sed5p in retrograde traffic to the cis-Golgi, despite the fact that recombinant Sed5p and Vti1p bind each other.…”

Section: Implication For the Role Of V-snares In Specificitymentioning

confidence: 99%

TheSaccharomyces cerevisiaev-SNARE Vti1p Is Required for Multiple Membrane Transport Pathways to the Vacuole

Mollard

Stevens

1999

MBoC

162

133

View full text Add to dashboard Cite

The interaction between v-SNAREs on transport vesicles and t-SNAREs on target membranes is required for membrane traffic in eukaryotic cells. Here we identify Vti1p as the first v-SNARE protein found to be required for biosynthetic traffic into the yeast vacuole, the equivalent of the mammalian lysosome. Certain vti1-tsyeast mutants are defective in alkaline phosphatase transport from the Golgi to the vacuole and in targeting of aminopeptidase I from the cytosol to the vacuole. VTI1 interacts genetically with the vacuolar t-SNARE VAM3, which is required for transport of both alkaline phosphatase and aminopeptidase I to the vacuole. The v-SNARE Nyv1p forms a SNARE complex with Vam3p in homotypic vacuolar fusion; however, we find that Nyv1p is not required for any of the three biosynthetic pathways to the vacuole. v-SNAREs were thought to ensure specificity in membrane traffic. However, Vti1p also functions in two additional membrane traffic pathways: Vti1p interacts with the t-SNAREs Pep12p in traffic from the TGN to the prevacuolar compartment and with Sed5p in retrograde traffic to the cis-Golgi. The ability of Vti1p to mediate multiple fusion steps requires additional proteins to ensure specificity in membrane traffic.

show abstract

“…Genetic analysis of the S. cerevisiae rab mutants ypt1 and sec4 demonstrates that certain rab molecules are essential for specific vesicular transport steps (for review, see Ferro-Novick and Novick, 1993). Furthermore, biochemical analysis with ypt1 mutant extracts suggests that the formation of biochemical complexes between vesicle proteins and proteins on the acceptor membranes requires rab proteins (Lian et al, 1994;Sogaard et al, 1994). These complexes are postulated to be postdocking intermediates in the vesicle fusion process .…”

mentioning

confidence: 99%

Caenorhabditis elegans rab-3Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

et al. 1997

View full text Add to dashboard Cite

Rab molecules regulate vesicular trafficking in many different exocytic and endocytic transport pathways in eukaryotic cells. In neurons, rab3 has been proposed to play a crucial role in regulating synaptic vesicle release. To elucidate the role of rab3 in synaptic transmission, we isolated and characterized Caenorhabditis elegans rab-3 mutants. Similar to the mouse rab3A mutants, these mutants survived and exhibited only mild behavioral abnormalities. In contrast to the mouse mutants, synaptic transmission was perturbed in these animals. Extracellular electrophysiological recordings revealed that synaptic transmission in the pharyngeal nervous system was impaired. Furthermore, rab-3 animals were resistant to the acetylcholinesterase inhibitor aldicarb, suggesting that cholinergic transmission was generally depressed. Last, synaptic vesicle populations were redistributed in rab-3 mutants. In motor neurons, vesicle populations at synapses were depleted to 40% of normal levels, whereas in intersynaptic regions of the axon, vesicle populations were elevated. On the basis of the morphological defects at neuromuscular junctions, we postulate that RAB-3 may regulate recruitment of vesicles to the active zone or sequestration of vesicles near release sites.

show abstract

A rab protein is required for the assembly of SNARE complexes in the docking of transport vesicles

Cited by 486 publications

References 55 publications

Genetic Analysis of SolubleN-Ethylmaleimide-Sensitive Factor Attachment Protein Function inDrosophilaReveals Positive and Negative Secretory Roles

Genetic Analysis of SolubleN-Ethylmaleimide-Sensitive Factor Attachment Protein Function inDrosophilaReveals Positive and Negative Secretory Roles

TheSaccharomyces cerevisiaev-SNARE Vti1p Is Required for Multiple Membrane Transport Pathways to the Vacuole

Caenorhabditis elegans rab-3Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

Contact Info

Product

Resources

About