A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport

Elife. 2015 May 22;4:e07253. doi: 10.7554/eLife.07253.

Abstract

Sterol traffic between the endoplasmic reticulum (ER) and plasma membrane (PM) is a fundamental cellular process that occurs by a poorly understood non-vesicular mechanism. We identified a novel, evolutionarily diverse family of ER membrane proteins with StART-like lipid transfer domains and studied them in yeast. StART-like domains from Ysp2p and its paralog Lam4p specifically bind sterols, and Ysp2p, Lam4p and their homologs Ysp1p and Sip3p target punctate ER-PM contact sites distinct from those occupied by known ER-PM tethers. The activity of Ysp2p, reflected in amphotericin-sensitivity assays, requires its second StART-like domain to be positioned so that it can reach across ER-PM contacts. Absence of Ysp2p, Ysp1p or Sip3p reduces the rate at which exogenously supplied sterols traffic from the PM to the ER. Our data suggest that these StART-like proteins act in trans to mediate a step in sterol exchange between the PM and ER.

Keywords: S. cerevisiae; StART protein; VASt domains; cell biology; cholesterol; ergosterol; lipid traffic; membrane contact sites; polyenes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / physiology
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Computational Biology
  • Endoplasmic Reticulum / metabolism*
  • HL-60 Cells
  • Humans
  • Mitochondrial Proteins / metabolism*
  • Plasmids / genetics
  • Polymerase Chain Reaction
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sterols / metabolism*

Substances

  • Carrier Proteins
  • Mitochondrial Proteins
  • Saccharomyces cerevisiae Proteins
  • Sterols
  • Ysp2 protein, S cerevisiae