Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin i

Dennis Koch, Isabella Spiwoks-Becker, Victor Sabanov, Anne Sinning, Tamar Dugladze, Anne Stellmacher, Rashmi Ahuja, Julia Grimm, Susann Schüler, Anke Müller, Frank Angenstein, Tariq Ahmed, Alexander Diesler, Markus Moser, Susanne Tom Dieck, Rainer Spessert, Tobias Maria Boeckers, Reinhard Fässler, Christian Andreas Hübner, Detlef BalschunTengis Gloveli, Michael Manfred Kessels, Britta Qualmann

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Synaptic transmission relies on effective and accurate compensatory endocytosis. F-BAR proteins may serve as membrane curvature sensors and/or inducers and thereby support membrane remodelling processes; yet, their in vivo functions urgently await disclosure. We demonstrate that the F-BAR protein syndapin I is crucial for proper brain function. Syndapin I knockout (KO) mice suffer from seizures, a phenotype consistent with excessive hippocampal network activity. Loss of syndapin I causes defects in presynaptic membrane trafficking processes, which are especially evident under high-capacity retrieval conditions, accumulation of endocytic intermediates, loss of synaptic vesicle (SV) size control, impaired activity-dependent SV retrieval and defective synaptic activity. Detailed molecular analyses demonstrate that syndapin I plays an important role in the recruitment of all dynamin isoforms, central players in vesicle fission reactions, to the membrane. Consistently, syndapin I KO mice share phenotypes with dynamin I KO mice, whereas their seizure phenotype is very reminiscent of fitful mice expressing a mutant dynamin. Thus, syndapin I acts as pivotal membrane anchoring factor for dynamins during regeneration of SVs.

Original languageEnglish
Pages (from-to)4955-4969
Number of pages15
JournalEMBO Journal
Volume30
Issue number24
DOIs
Publication statusPublished - 14 Dec 2011

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Keywords

  • F-BAR protein syndapin/PACSIN
  • SV formation and recycling
  • membrane recruitment of dynamins
  • rod photoreceptor ribbon synapses
  • seizures with tonic-clonic convulsions

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Koch, D., Spiwoks-Becker, I., Sabanov, V., Sinning, A., Dugladze, T., Stellmacher, A., Ahuja, R., Grimm, J., Schüler, S., Müller, A., Angenstein, F., Ahmed, T., Diesler, A., Moser, M., Tom Dieck, S., Spessert, R., Boeckers, T. M., Fässler, R., Hübner, C. A., ... Qualmann, B. (2011). Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin i. EMBO Journal, 30(24), 4955-4969. https://doi.org/10.1038/emboj.2011.339