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Endocytosis and clathrin-uncoating defects at synapses of auxilin knockout mice.

Neuronally expressed auxilin and ubiquitously expressed cyclin-G-dependent kinase (GAK) are homologous proteins that act as cochaperones to support the Hsc70-dependent clathrin uncoating of clathrin-coated vesicles. GAK was previously shown to be essential in mouse during embryonic development and in the adult. We have now engineered an auxilin knockout mouse. Mutant mice had a high rate of early postnatal mortality and surviving pups generally had a lower body weight than wild-type pups, although they had a normal life span. GAK was up-regulated as much as 3-fold in the brains of both surviving neonates and adult mutant mice. An increased number of clathrin-coated vesicles and empty cages were present at knockout synapses both in situ and in primary neuronal cultures. Additionally, clathrin-mediated endocytosis of synaptic vesicles in knockout hippocampal neurons was impaired, most likely due to sequestration of coat components in assembled coats and cages. Collectively, our results demonstrate the specialized role of auxilin in the recycling of synaptic vesicles at synapses, but also show that its function can be partially compensated for by up-regulation of GAK.

Pubmed ID: 20160091

Authors

  • Yim YI
  • Sun T
  • Wu LG
  • Raimondi A
  • De Camilli P
  • Eisenberg E
  • Greene LE

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 2, 2010

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA018343
  • Agency: NINDS NIH HHS, Id: NS36251
  • Agency: NIDA NIH HHS, Id: P30 DA018343
  • Agency: NINDS NIH HHS, Id: R37 NS036251
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Auxilins
  • Clathrin
  • Endocytosis
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Endings
  • Protein-Serine-Threonine Kinases
  • Synapses
  • Up-Regulation