Regulation of Clathrin-Mediated Endocytosis

Annu Rev Biochem. 2018 Jun 20;87:871-896. doi: 10.1146/annurev-biochem-062917-012644. Epub 2018 Apr 16.


Clathrin-mediated endocytosis (CME) is the major endocytic pathway in mammalian cells. It is responsible for the uptake of transmembrane receptors and transporters, for remodeling plasma membrane composition in response to environmental changes, and for regulating cell surface signaling. CME occurs via the assembly and maturation of clathrin-coated pits that concentrate cargo as they invaginate and pinch off to form clathrin-coated vesicles. In addition to the major coat proteins, clathrin triskelia and adaptor protein complexes, CME requires a myriad of endocytic accessory proteins and phosphatidylinositol lipids. CME is regulated at multiple steps-initiation, cargo selection, maturation, and fission-and is monitored by an endocytic checkpoint that induces disassembly of defective pits. Regulation occurs via posttranslational modifications, allosteric conformational changes, and isoform and splice-variant differences among components of the CME machinery, including the GTPase dynamin. This review summarizes recent findings on the regulation of CME and the evolution of this complex process.

Keywords: AP2; adaptor protein-2; dynamin; endocytic accessory proteins; endocytic checkpoint; evolution; signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Protein Complex 2 / chemistry
  • Adaptor Protein Complex 2 / metabolism
  • Allosteric Regulation
  • Animals
  • Clathrin / chemistry
  • Clathrin / metabolism*
  • Clathrin-Coated Vesicles / metabolism
  • Dynamins / chemistry
  • Dynamins / metabolism
  • Endocytosis / physiology*
  • Evolution, Molecular
  • Humans
  • Models, Biological
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphorylation
  • Protein Conformation
  • Signal Transduction


  • Adaptor Protein Complex 2
  • Clathrin
  • Phosphatidylinositol Phosphates
  • Dynamins