Choline transport activity regulates phosphatidylcholine synthesis through choline transporter Hnm1 stability

J Biol Chem. 2013 Dec 13;288(50):36106-15. doi: 10.1074/jbc.M113.499855. Epub 2013 Nov 1.

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.

Keywords: Glycerophospholipid; Membrane Transport; Phosphatidylcholine; Phospholipid Metabolism; Yeast Metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport, Active
  • Choline / metabolism*
  • Down-Regulation
  • Endocytosis
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism*
  • Mutation
  • Phosphatidylcholines / biosynthesis*
  • Protein Stability
  • Protein Transport
  • Proteolysis
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Ubiquitin-Protein Ligase Complexes / metabolism
  • Vacuoles / metabolism

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Membrane Transport Proteins
  • Phosphatidylcholines
  • Saccharomyces cerevisiae Proteins
  • choline transporter
  • Ubiquitin-Protein Ligase Complexes
  • RSP5 protein, S cerevisiae
  • Choline