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Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice.


The function of the clathrin coat in synaptic vesicle endocytosis is assisted by a variety of accessory factors, among which amphiphysin (amphiphysin 1 and 2) is one of the best characterized. A putative endocytic function of amphiphysin was supported by dominant-negative interference studies. We have now generated amphiphysin 1 knockout mice and found that lack of amphiphysin 1 causes a parallel dramatic reduction of amphiphysin 2 selectively in brain. Cell-free assembly of endocytic protein scaffolds is defective in mutant brain extracts. Knockout mice exhibit defects in synaptic vesicle recycling that are unmasked by stimulation and suggest impairments at multiple stages of the cycle. These defects correlate with increased mortality due to rare irreversible seizures and with major learning deficits, suggesting a critical role of amphiphysin for higher brain functions.

Pubmed ID: 11879655


  • Di Paolo G
  • Sankaranarayanan S
  • Wenk MR
  • Daniell L
  • Perucco E
  • Caldarone BJ
  • Flavell R
  • Picciotto MR
  • Ryan TA
  • Cremona O
  • De Camilli P



Publication Data

February 28, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA46128
  • Agency: Telethon, Id: D.111
  • Agency: NIDA NIH HHS, Id: DA00436
  • Agency: NIGMS NIH HHS, Id: GM61925
  • Agency: NIMH NIH HHS, Id: MH25642
  • Agency: NINDS NIH HHS, Id: NS24692
  • Agency: NINDS NIH HHS, Id: NS36251

Mesh Terms

  • Animals
  • Cerebral Cortex
  • Clathrin
  • Conditioning, Classical
  • Endocytosis
  • Fluorescent Dyes
  • GABA Antagonists
  • Glutamic Acid
  • Humans
  • Maze Learning
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Neurons
  • Pentylenetetrazole
  • Protein Isoforms
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Survival Rate
  • Synaptic Vesicles