The role of molecular chaperones in clathrin mediated vesicular trafficking

Rui Sousa, Eileen M. Lafer

Research output: Contribution to journalShort surveypeer-review

32 Scopus citations

Abstract

The discovery that the 70 kD "uncoating ATPase," which removes clathrin coats from vesicles after endocytosis, is the constitutively expressed Hsc70 chaperone was a surprise. Subsequent work, however, revealed that uncoating is an archetypal Hsp70 reaction: the cochaperone auxilin, which contains a clathrin binding domain and an Hsc70 binding J domain, recruits Hsc70*ATP to the coat and, concomitant with ATP hydrolysis, transfers it to a hydrophobic Hsc70-binding element found on a flexible tail at the C-terminus of the clathrin heavy chain. Release of clathrin in association with Hsc70*ADP follows, and the subsequent, persistent association of clathrin with Hsc70 is important to prevent aberrant clathrin polymerization. Thus, the two canonical functions of Hsp70-dissociation of existing protein complexes or aggregates, and binding to a protein to inhibit its inappropriate aggregation-are recapitulated in uncoating. Association of clathrin with Hsc70 in vivo is regulated by Hsp110, an Hsp70 NEF that is itself a member of the Hsp70 family. How Hsp110 activity is itself regulated to make Hsc70-free clathrin available for endocytosis is unclear, though at synapses it's possible that the influx of calcium that accompanies depolarization activates the Ca++/calmodulin dependent calcineurin phosphatase which then dephosphorylates and activates Hsp110 to stimulate ADP/ATP exchange and release clathrin from Hsc70*ADP:clathrin complexes.

Original languageEnglish (US)
Article number26
JournalFrontiers in Molecular Biosciences
Volume2
Issue numberMAY
DOIs
StatePublished - May 19 2015

Keywords

  • Auxilin
  • Chaperone
  • Clathrin
  • Endocytosis
  • Hsc70
  • Hsp110
  • Hsp70
  • NEF

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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