title: Choline transport activity regulates phosphatidylcholine synthesis through choline transporter Hnm1 stability.
abstract: Choline is a precursor for the synthesis of phosphatidylcholine through the CDP-choline pathway. Saccharomyces cerevisiae expresses a single high affinity choline transporter at the plasma membrane, encoded by the HNM1 gene. We show that exposing cells to increasing levels of choline results in two different regulatory mechanisms impacting Hnm1 activity. Initial exposure to choline results in a rapid decrease in Hnm1-mediated transport at the level of transporter activity, whereas chronic exposure results in Hnm1 degradation through an endocytic mechanism that depends on the ubiquitin ligase Rsp5 and the casein kinase 1 redundant pair Yck1/Yck2. We present details of how the choline transporter is a major regulator of phosphatidylcholine synthesis.
authors.affiliation: From the Department of Pharmacology, Atlantic Research Centre, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
authors.forename: J Pedro
authors.initials: JP
authors.lastname: Fernández-Murray
authors.forename: Michael H
authors.initials: MH
authors.lastname: Ngo
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McMaster
mesh_terms: D001693:Biological Transport, Active; D002794:Choline / Q000378:metabolism*; D015536:Down-Regulation; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D009154:Mutation; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D055550:Protein Stability; D021381:Protein Transport; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D026901:Membrane Transport Proteins; D010713:Phosphatidylcholines; D029701:Saccharomyces cerevisiae Proteins; C065637:choline transporter; D043743:Ubiquitin-Protein Ligase Complexes; C469287:RSP5 protein, S cerevisiae; D002794:Choline
keywords: Glycerophospholipid; Membrane Transport; Phosphatidylcholine; Phospholipid Metabolism; Yeast Metabolism