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

  • Di Paolo G
  • Sankaranarayanan S
  • Wenk M
 et al. 
  • 112

    Readers

    Mendeley users who have this article in their library.
  • 163

    Citations

    Citations of this article.

Abstract

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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Gilbert Di Paolo

  • Sethuraman Sankaranarayanan

  • Markus R. Wenk

  • Laurie Daniell

  • Ezio Perucco

  • Barbara J. Caldarone

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free