title: An assembly of proteins and lipid domains regulates transport of phosphatidylserine to phosphatidylserine decarboxylase 2 in Saccharomyces cerevisiae.
abstract: Saccharomyces cerevisiae uses multiple biosynthetic pathways for the synthesis of phosphatidylethanolamine. One route involves the synthesis of phosphatidylserine (PtdSer) in the endoplasmic reticulum (ER), the transport of this lipid to endosomes, and decarboxylation by PtdSer decarboxylase 2 (Psd2p) to produce phosphatidylethanolamine. Several proteins and protein motifs are known to be required for PtdSer transport to occur, namely the Sec14p homolog PstB2p/Pdr17p; a PtdIns 4-kinase, Stt4p; and a C2 domain of Psd2p. The focus of this work is on defining the protein-protein and protein-lipid interactions of these components. PstB2p interacts with a protein encoded by the uncharacterized gene YPL272C, which we name Pbi1p (PstB2p-interacting 1). PstB2p, Psd2, and Pbi1p were shown to be lipid-binding proteins specific for phosphatidic acid. Pbi1p also interacts with the ER-localized Scs2p, a binding determinant for several peripheral ER proteins. A complex between Psd2p and PstB2p was also detected, and this interaction was facilitated by a cryptic C2 domain at the extreme N terminus of Psd2p (C2-1) as well the previously characterized C2 domain of Psd2p (C2-2). The predicted N-terminal helical region of PstB2p was necessary and sufficient for promoting the interaction with both Psd2p and Pbi1p. Taken together, these results support a model for PtdSer transport involving the docking of a PtdSer donor membrane with an acceptor via specific protein-protein and protein-lipid interactions. Specifically, our model predicts that this process involves an acceptor membrane complex containing the C2 domains of Psd2p, PstB2p, and Pbi1p that ligate to Scs2p and phosphatidic acid present in the donor membrane, forming a zone of apposition that facilitates PtdSer transfer.
authors.affiliation: From the Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, Colorado 80206 and.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Riekhof
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Wu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Jones
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Nikrad
authors.forename: Mallory M
authors.initials: MM
authors.lastname: Chan
authors.forename: Christopher J R
authors.initials: CJ
authors.lastname: Loewen
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
mesh_terms: D001693:Biological Transport, Active / Q000502:physiology; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010718:Phosphatidylserines / Q000235:genetics / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000235:genetics; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D046912:Multiprotein Complexes; C492205:PDR17 protein, S cerevisiae; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D029701:Saccharomyces cerevisiae Proteins; C501314:Scs2 protein, S cerevisiae; D002262:Carboxy-Lyases; C022353:phosphatidylserine decarboxylase
keywords: Endoplasmic Reticulum (ER); Endosomes; Glycerophospholipid; Lipid Transport; Membrane Biogenesis; Phosphatidic Acid; Phosphatidylethanolamine; Phosphatidylserine; Yeast