title: Palmitoylation by the DHHC protein Pfa4 regulates the ER exit of Chs3.
abstract: The yeast chitin synthase Chs3 provides a well-studied paradigm for polytopic membrane protein trafficking. In this study, high-throughput analysis of the yeast deletion collection identifies a requirement for Pfa4, which is an uncharacterized protein with protein acyl transferase (PAT) homology, in Chs3 transport. PATs, which are the enzymatic mediators of protein palmitoylation, have only recently been discovered, and few substrates have been identified. We find that Chs3 is palmitoylated and that this modification is Pfa4-dependent, indicating that Pfa4 is indeed a PAT. Chs3 palmitoylation is required for ER export, but not for interaction with its dedicated ER chaperone, Chs7. Nonetheless, both palmitoylation and chaperone association are required to prevent the accumulation of Chs3 in high-molecular mass aggregates at the ER. Our data indicate that palmitoylation is necessary for Chs3 to attain an export-competent conformation, and suggest the possibility of a more general role for palmitoylation in the ER quality control of polytopic membrane proteins.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Karen K Y
authors.initials: KK
authors.lastname: Lam
authors.forename: Michael
authors.initials: M
authors.lastname: Davey
authors.forename: Beimeng
authors.initials: B
authors.lastname: Sun
authors.forename: Amy F
authors.initials: AF
authors.lastname: Roth
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Davis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Conibear
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D002687:Chitin Synthase; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D019308:Palmitic Acid; D000217:Acyltransferases; C511958:Pfa4 protein, S cerevisiae; C069390:CHS3 protein, S cerevisiae; D002687:Chitin Synthase