ELKS2α/CAST Deletion Selectively Increases Neurotransmitter Release at Inhibitory Synapses

Pascal S. Kaeser, Lunbin Deng, Andrés E. Chávez, Xinran Liu, Pablo E. Castillo, Thomas C. Südhof

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

The presynaptic active zone is composed of a protein network that contains ELKS2α (a.k.a. CAST) as a central component. Here we demonstrate that in mice, deletion of ELKS2α caused a large increase in inhibitory, but not excitatory, neurotransmitter release, and potentiated the size, but not the properties, of the readily-releasable pool of vesicles at inhibitory synapses. Quantitative electron microscopy revealed that the ELKS2α deletion did not change the number of docked vesicles or other ultrastructural parameters of synapses, except for a small decrease in synaptic vesicle numbers. The ELKS2α deletion did, however, alter the excitatory/inhibitory balance and exploratory behaviors, possibly as a result of the increased synaptic inhibition. Thus, as opposed to previous studies indicating that ELKS2α is essential for mediating neurotransmitter release, our results suggest that ELKS2α normally restricts release and limits the size of the readily-releasable pool of synaptic vesicles at the active zone of inhibitory synapses.

Original languageEnglish (US)
Pages (from-to)227-239
Number of pages13
JournalNeuron
Volume64
Issue number2
DOIs
StatePublished - Oct 29 2009

Keywords

  • CELLBIO
  • MOLIMMUNO
  • SIGNALING

ASJC Scopus subject areas

  • General Neuroscience

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