Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel. Academic Article uri icon

Overview

MeSH

  • Animals
  • Binding Sites
  • Chlorides
  • Humans
  • Ion Channel Gating
  • Ion Transport
  • Ions
  • Lipid Metabolism
  • Mammals

MeSH Major

  • Aspergillus fumigatus
  • Calcium
  • Calcium Channels
  • Fungal Proteins
  • Phospholipid Transfer Proteins
  • Phospholipids

abstract

  • Phospholipid (PL) scramblases disrupt the lipid asymmetry of the plasma membrane, externalizing phosphatidylserine to trigger blood coagulation and mark apoptotic cells. Recently, members of the TMEM16 family of Ca(2+)-gated channels have been shown to be involved in Ca(2+)-dependent scrambling. It is however controversial whether they are scramblases or channels regulating scrambling. Here we show that purified afTMEM16, from Aspergillus fumigatus, is a dual-function protein: it is a Ca(2+)-gated channel, with characteristics of other TMEM16 homologues, and a Ca(2+)-dependent scramblase, with the expected properties of mammalian PL scramblases. Remarkably, we find that a single Ca(2+) site regulates separate transmembrane pathways for ions and lipids. Two other purified TMEM16-channel homologues do not mediate scrambling, suggesting that the family diverged into channels and channel/scramblases. We propose that the spatial separation of the ion and lipid pathways underlies the evolutionary divergence of the TMEM16 family, and that other homologues, such as TMEM16F, might also be dual-function channel/scramblases.

publication date

  • 2013

has subject area

  • Animals
  • Aspergillus fumigatus
  • Binding Sites
  • Calcium
  • Calcium Channels
  • Chlorides
  • Fungal Proteins
  • Humans
  • Ion Channel Gating
  • Ion Transport
  • Ions
  • Lipid Metabolism
  • Mammals
  • Phospholipid Transfer Proteins
  • Phospholipids

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3970400

Digital Object Identifier (DOI)

  • 10.1038/ncomms3367

PubMed ID

  • 23996062

Additional Document Info

start page

  • 2367

volume

  • 4