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

Gilbert Di Paolo, Sethuraman Sankaranarayanan, Markus R. Wenk, Laurie Daniell, Ezio Perucco, Barbara J. Caldarone, Richard Flavell, Marina R. Picciotto, Timothy A. Ryan, Ottavio Cremona, Pietro De Camilli

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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.

Original languageEnglish
Pages (from-to)789-804
Number of pages16
JournalNeuron
Volume33
Issue number5
DOIs
Publication statusPublished - Feb 28 2002

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Di Paolo, G., Sankaranarayanan, S., Wenk, M. R., Daniell, L., Perucco, E., Caldarone, B. J., Flavell, R., Picciotto, M. R., Ryan, T. A., Cremona, O., & De Camilli, P. (2002). Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron, 33(5), 789-804. https://doi.org/10.1016/S0896-6273(02)00601-3