Swf1-dependent palmitoylation of the SNARE Tlg1 prevents its ubiquitination and degradation.
Protein palmitoylation is a post-translational modification that affects a great number of proteins. In most cases, the enzymes responsible for this modification have not been identified. Some proteins use palmitoylation to attach themselves to membranes; however, palmitoylation also occurs in transmembrane proteins, and the function of this palmitoylation is less clear. Here we identify Swf1, a member of the DHHC-CDR family of palmitoyltransferases, as the protein responsible for modifying the yeast SNAREs Snc1, Syn8 and Tlg1, at cysteine residues close to the cytoplasmic end of their single transmembrane domains (TMDs). In an swf1Delta mutant, Tlg1 is mis-sorted to the vacuole. This occurs because unpalmitoylated Tlg1 is recognised by the ubiquitin ligase Tul1, resulting in its targeting to the multivesicular body pathway. Our results suggest that one role of palmitoylation is to protect TMDs from the cellular quality control machinery, and that Swf1 may be the enzyme responsible for most, if not all, TMD-associated palmitoylation in yeast.
MRC Laboratory of Molecular Biology, Cambridge, UK.
Javier
J
Valdez-Taubas
Hugh
H
Pelham
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D019308:Palmitic Acid / Q000378:metabolism*; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D008565:Membrane Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; C083241:SNC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C503584:Tlg1 protein, S cerevisiae; D025801:Ubiquitin; D033921:Vesicular Transport Proteins; D019308:Palmitic Acid; D000217:Acyltransferases; C503585:Swf1 protein, S cerevisiae; D002334:Carnitine O-Palmitoyltransferase; C461959:TUL1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases