Cellular and molecular interactions of phosphoinositides and peripheral proteins

Robert V. Stahelin, Jordan L. Scott, Cary T. Frick

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Anionic lipids act as signals for the recruitment of proteins containing cationic clusters to biological membranes. A family of anionic lipids known as the phosphoinositides (PIPs) are low in abundance, yet play a critical role in recruitment of peripheral proteins to the membrane interface. PIPs are mono-, bis-, or trisphosphorylated derivatives of phosphatidylinositol (PI) yielding seven species with different structure and anionic charge. The differential spatial distribution and temporal appearance of PIPs is key to their role in communicating information to target proteins. Selective recognition of PIPs came into play with the discovery that the substrate of protein kinase C termed pleckstrin possessed the first PIP binding region termed the pleckstrin homology (PH) domain. Since the discovery of the PH domain, more than ten PIP binding domains have been identified including PH, ENTH, FYVE, PX, and C2 domains. Representative examples of each of these domains have been thoroughly characterized to understand how they coordinate PIP headgroups in membranes, translocate to specific membrane docking sites in the cell, and function to regulate the activity of their full-length proteins. In addition, a number of novel mechanisms of PIP-mediated membrane association have emerged, such as coincidence detection-specificity for two distinct lipid headgroups. Other PIP-binding domains may also harbor selectivity for a membrane physical property such as charge or membrane curvature. This review summarizes the current understanding of the cellular distribution of PIPs and their molecular interaction with peripheral proteins.

Original languageEnglish (US)
Pages (from-to)3-18
Number of pages16
JournalChemistry and Physics of Lipids
Volume182
DOIs
StatePublished - Sep 2014

Fingerprint

Molecular interactions
Phosphatidylinositols
Membranes
Proteins
Lipids
Biological membranes
Ports and harbors
Protein Kinase C
Spatial distribution
Membrane Proteins
Physical properties
Derivatives
platelet protein P47
Substrates

Keywords

  • C2 domain
  • FYVE domain
  • Lipid binding
  • Membrane binding
  • Peripheral protein
  • PH domain
  • Phosphoinsoitide
  • PI(3)P

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology
  • Medicine(all)

Cite this

Cellular and molecular interactions of phosphoinositides and peripheral proteins. / Stahelin, Robert V.; Scott, Jordan L.; Frick, Cary T.

In: Chemistry and Physics of Lipids, Vol. 182, 09.2014, p. 3-18.

Research output: Contribution to journalArticle

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