Phosphoinositide control of membrane protein function: A frontier led by studies on ion channels

Diomedes E. Logothetis, Vasileios I. Petrou, Miao Zhang, Rahul Mahajan, Xuan Yu Meng, Scott K. Adney, Meng Cui, Lia Baki

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Anionic phospholipids are critical constituents of the inner leaflet of the plasma membrane, ensuring appropriate membrane topology of transmembrane proteins. Additionally, in eukaryotes, the negatively charged phosphoinositides serve as key signals not only through their hydrolysis products but also through direct control of transmembrane protein function. Direct phosphoinositide control of the activity of ion channels and transporters has been the most convincing case of the critical importance of phospholipid-protein interactions in the functional control of membrane proteins. Furthermore, second messengers, such as [Ca2+]i, or posttranslational modifications, such as phosphorylation, can directly or allosterically fine-tune phospholipid-protein interactions and modulate activity. Recent advances in structure determination of membrane proteins have allowed investigators to obtain complexes of ion channels with phosphoinositides and to use computational and experimental approaches to probe the dynamic mechanisms by which lipid-protein interactions control active and inactive protein states.

Original languageEnglish (US)
Pages (from-to)81-104
Number of pages24
JournalAnnual review of physiology
Volume77
DOIs
StatePublished - Feb 1 2015

Keywords

  • Ion channels
  • Modulation
  • P
  • P-induced gating
  • PI(4,5)
  • Phosphoinositides
  • Phosphorylation

ASJC Scopus subject areas

  • Physiology

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