Septins regulate developmental switching from microdomain to nanodomain coupling of Ca2+ influx to neurotransmitter release at a central synapse

Yi Mei Yang, Michael J. Fedchyshyn, Giovanbattista Grande, Jamila Aitoubah, Christopher W. Tsang, Hong Xie, Cameron A. Ackerley, William S. Trimble, Lu Yang Wang

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Neurotransmitter release depends critically on close spatial coupling of Ca2+ entry to synaptic vesicles at the nerve terminal; however, the molecular substrates determining their physical proximity are unknown. Using the calyx of Held synapse, where "microdomain" coupling predominates at immature stages and developmentally switches to "nanodomain" coupling, we demonstrate that deletion of the filamentous protein Septin 5 imparts immature synapses with striking morphological and functional features reminiscent of mature synapses. This includes synaptic vesicles tightly localized to active zones, resistance to the slow Ca2+ buffer EGTA and a reduced number of Ca2+ channels required to trigger single fusion events. Disrupting Septin 5 organization acutely transforms microdomain to nanodomain coupling and potentiates quantal output in immature wild-type terminals. These observations suggest that Septin 5 is a core molecular substrate that differentiates distinct release modalities at the central synapse.

Original languageEnglish (US)
Pages (from-to)100-115
Number of pages16
JournalNeuron
Volume67
Issue number1
DOIs
StatePublished - Jul 2010

Bibliographical note

Funding Information:
This work was supported by individual operating grants (MOP-143867 and MOP-97950) from Canadian Institutes of Health Research (CIHR) (to L.-Y.W. and W.S.T., respectively). W.S.T. and L.-Y.W. are the recipients of Canada Research Chairs. We thank Drs. Milton Charlton and Harold Atwood for critically reviewing an early version of this paper and other members of the Wang and Trimble labs for technical assistance, comments and discussions.

Keywords

  • Molneuro
  • Signaling
  • Sysneuro

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