Diversity of Clathrin Function: New Tricks for an Old Protein

Annu Rev Cell Dev Biol. 2012;28:309-36. doi: 10.1146/annurev-cellbio-101011-155716. Epub 2012 Jul 23.

Abstract

Clathrin is considered the prototype vesicle coat protein whose self-assembly mediates sorting of membrane cargo and recruitment of lipid modifiers. Detailed knowledge of clathrin biochemistry, structure, and interacting proteins has accumulated since the first observation, almost 50 years ago, of its role in receptor-mediated endocytosis of yolk protein. This review summarizes that knowledge, and focuses on properties of the clathrin heavy and light chain subunits and interaction of the latter with Hip proteins, to address the diversity of clathrin function beyond conventional receptor-mediated endocytosis. The distinct functions of the two human clathrin isoforms (CHC17 and CHC22) are discussed, highlighting CHC22's specialized involvement in traffic of the GLUT4 glucose transporter and consequent role in human glucose metabolism. Analysis of clathrin light chain function and interaction with the actin-binding Hip proteins during bacterial infection defines a novel actin-organizing function for CHC17 clathrin. By considering these diverse clathrin functions, along with intracellular sorting roles and influences on mitosis, further relevance of clathrin function to human health and disease is established.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Clathrin / chemistry
  • Clathrin / genetics
  • Clathrin / physiology*
  • Clathrin-Coated Vesicles / metabolism
  • Clathrin-Coated Vesicles / physiology
  • Cytoskeleton / metabolism
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary

Substances

  • Clathrin
  • Protein Isoforms