High impact information on SNC1

• The yeast S. cerevisiae possesses two genes, SNC1 and SNC2, that encode homologs of vertebrate synaptic vesicle-associated membrane proteins, also known as synaptobrevins [1].
• Endocytic recycling and slow diffusion on the plasma membrane were shown to facilitate polarized surface distribution of Snc1p (Valdez-Taubas, J., and H.R. Pelham. 2003. Curr. Biol. 13:1636-1640) [2].
• Snx4p binds to Snx41p/ydr425w and to Snx42p/ydl113c, both of which are also required for efficient Snc1p sorting [3].
• In contrast, retrieval of Snc1p from post-Golgi endosomes requires the sorting nexin Snx4p, to which Snc1p can be cross-linked [3].
• The endocytic pathway in yeast leads to the vacuole, but resident proteins of the late Golgi, and some endocytosed proteins such as the exocytic SNARE Snc1p, are retrieved specifically to the Golgi [3].

Biological context of SNC1

• As no v-SNARE has been shown to confer endocytosis, we examined whether yeast lacking the SNC genes, or possessing a temperature-sensitive allele of SNC1 (SNC1(ala43)), are deficient in the endocytic uptake of components from the cell surface [4].
• We isolated Btn2 as a Snc1 v-SNARE binding protein using the two-hybrid assay and examined its role in intracellular protein trafficking [5].
• Multicopy plasmids expressing SNC1 suppress only the loss of the C-terminal functions of CAP and only in the presence of activated RAS2 [6].
• High-level expression of mutant Snc1 or Sso2 proteins that have a COOH-terminal geranylgeranylation signal instead of a transmembrane domain inhibits exocytosis at a stage after vesicle docking [7].
• Here we demonstrate that Snc proteins undergo a single posttranslational modification with the addition of a palmitate moiety to Cys-95 in Snc1 [8].

Anatomical context of SNC1

• In yeast, homologues of the synaptobrevin/VAMP family of v-SNAREs (Snc1 and Snc2) confer the docking and fusion of secretory vesicles at the cell surface [4].
• The v-SNARE proteins Snc1p and Snc2p are required for fusion of secretory vesicles with the plasma membrane in yeast [9].
• Interestingly, recycling of GFP-Snc1p in gyp1 Delta cells is partially restored by reducing the activity of Ypt1p [10].
• We propose that these represent early endosomes in which sorting of Snc1p and late Golgi proteins occurs, and that transport can occur directly from them to the Golgi apparatus [11].
• The Cdc50p-depleted gga1Delta gga2Delta mutant and the gcs1Delta apl2Delta (the beta1 subunit of AP-1) mutant exhibited growth defects and intracellular Snc1p-containing membranes accumulated in these cells [12].

Associations of SNC1 with chemical compounds

• The overexpression of SNC1 was used to achieve the depletion of the palmitoyl-CoA pool, because the loss of Snc palmitoylation does not affect the general growth characteristics of yeast and does not interfere with the secretory processes (Couve, A. et al., Proc. Natl. Acad. Sci. USA, 92, 5987-5991 (1995)) [13].
• Although the sake yeast UT-1 exhibited much better growth in the presence of ethanol than laboratory strains, the overexpression of Snc1 was accompanied by sparse growth with increasing ethanol concentration [13].
• Exogenous palmitic acid rescued the poor growth caused by Snc1 overexpression, and the overexpression of Snc1(ser95) (which could not palmitoylated) had no effect on the growth characteristics of strain UT-1, suggesting that the poor growth with Snc1 overexpression was due to an overall increase in proteins in the unpalmitoylated form [13].
• To ascertain that fatty acid activation has a distinct role in the growth of yeast in the presence of ethanol, FAA genes encoding long chain acyl-CoA synthetases were overexpressed in combination with snc1 overexpression [13].
• The cdc50-ts mutants did not exhibit major defects in the exocytic pathways, but they did exhibit those in endocytic recycling; large membranous structures containing the vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor Snc1p intracellularly accumulated in these mutants [14].

Physical interactions of SNC1

• However, as a hetero-oligomeric complex, Sec9 and Sso1 show strong binding to Snc1 [15].
• Skp1p and the F-box protein Rcy1p form a non-SCF complex involved in recycling of the SNARE Snc1p in yeast [16].
• Tlg1p also binds the plasma membrane v-SNARE Snc1p [17].
• Finally, we show that Rcy1 physically interacts with Snc1 [18].

Other interactions of SNC1

• Conversely, overexpression of Gyp2p in wild-type cells interferes with recycling of GFP-Snc1p, and the cells accumulate membrane structures as evidenced by electron microscopy [19].
• The most striking difference we have found between the yeast and neuronal proteins is that individually neither of the target membrane SNAREs (t-SNAREs), Sso1 nor Sec9, show any detectable binding to the synaptobrevin homolog, Snc1 [15].
• We report here the first biochemical characterization of a nonneuronal SNARE complex using recombinant forms of the yeast exocytic SNARE proteins Snc1, Sso1, and Sec9 and the yeast alpha-SNAP homolog, Sec17 [15].
• Here we show that the F-box protein Rcy1p is required for recycling of the v-SNARE Snc1p in Saccharomyces cerevisiae [16].
• In the gga1 gga2 double mutant endogenous Pep12p cofractionated with the early endosome marker Tlg1p, and recycling of Snc1p through early endosomes was defective [20].

References