Turning CALM into excitement: AP180 and CALM in endocytosis and disease

Biol Cell. 2012 Oct;104(10):588-602. doi: 10.1111/boc.201200008. Epub 2012 May 31.

Abstract

Dynamic flux of membrane between intracellular compartments is a key feature of all eukaryotic cells. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) play a crucial role in membrane dynamics by facilitating membrane fusion, for example at synapses where small synaptic vesicles (SVs) undergo activity-regulated neuroexocytosis, followed by the endocytic re-cycling of SV proteins and lipids. Recent work shows that the assembly protein 180 (AP180) N-terminal homology (ANTH) domain containing proteins AP180 and clathrin assembly lymphoid myeloid leukaemia (CALM) not only regulate the assembly of the endocytic machinery but also act as sorters for a subset of SNAREs, the vesicle-associated membrane proteins (VAMPs), most notably VAMP/synaptobrevin 2 at synapses. In this review, we summarise the current state of knowledge about the roles of AP180 and CALM family members in clathrin-dependent membrane traffic, the molecular mechanistic basis for their activities and their potential involvement in human disease.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Clathrin / genetics
  • Clathrin / metabolism
  • Endocytosis / physiology*
  • Exocytosis / physiology
  • Humans
  • Membrane Fusion
  • Mice
  • Monomeric Clathrin Assembly Proteins / genetics
  • Monomeric Clathrin Assembly Proteins / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism*
  • Synaptic Vesicles / genetics
  • Synaptic Vesicles / metabolism*
  • Vesicle-Associated Membrane Protein 2 / genetics
  • Vesicle-Associated Membrane Protein 2 / metabolism

Substances

  • Clathrin
  • Monomeric Clathrin Assembly Proteins
  • PICALM protein, human
  • SNARE Proteins
  • Vesicle-Associated Membrane Protein 2
  • clathrin assembly protein AP180