Phosphoinositides in endocytosis

Biochim Biophys Acta. 2015 Jun;1851(6):794-804. doi: 10.1016/j.bbalip.2014.09.014. Epub 2014 Sep 28.


The internalization and subsequent endosomal trafficking of proteins and membrane along the endocytic pathway is a fundamental cellular process. Over the last two decades, this pathway has emerged to be subject to extensive regulation by phosphoinositides (PIs), phosphorylated derivatives of the minor membrane phospholipid phosphatidylinositol. Clathrin-mediated endocytosis (CME) is the endocytic mechanism characterized in most detail. It now represents a prime example of a process spatiotemporally organized by the interplay of PI metabolizing enzymes. The most abundant PI, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P₂], serves as a denominator of plasma membrane identity and together with cargo proteins is instrumental for the initiation of clathrin-coated pit (CCP) formation. During later stages of the process, the generation of phosphatidylinositol-3,4-bisphosphate [PI(3,4)P₂] and the dephosphorylation of PI(4,5)P₂regulate CCP maturation and vesicle uncoating. Here we provide an overview of the mechanisms by which PIs are made and consumed to regulate CME and other endocytic pathways and how conversion of PIs en route to endosomes may be accomplished. Mutations in PI converting enzymes are linked to multiple diseases ranging from mental retardation and neurodegeneration, to inherited muscle and kidney disorders suggesting that the tight control of PI levels along the endocytic pathway plays a critical role in cell physiology. This article is part of a Special Issue entitled Phosphoinositides.

Keywords: CLIC/GEEC; Clathrin; Endocytosis; Endosome; Phosphatidylinositol-3,4-bisphosphate; Phosphatidylinositol-4,5-bisphosphate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Clathrin / genetics
  • Clathrin / metabolism*
  • Clathrin-Coated Vesicles / chemistry
  • Clathrin-Coated Vesicles / metabolism
  • Coated Pits, Cell-Membrane / chemistry
  • Coated Pits, Cell-Membrane / metabolism
  • Endocytosis / genetics*
  • Endosomes / chemistry
  • Endosomes / metabolism
  • Gene Expression Regulation
  • Humans
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Phosphatidylinositol Phosphates / metabolism
  • Signal Transduction


  • Adaptor Proteins, Vesicular Transport
  • Clathrin
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 3,4-diphosphate