RIM1α and RIM1β are synthesized from distinct promoters of the RIM1 gene to mediate differential but overlapping synaptic functions

Pascal S. Kaeser, Hyung Bae Kwon, Chiayu Q. Chiu, Lunbin Deng, Pablo E. Castillo, Thomas C. Südhof

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

At a synapse, presynaptic terminals form a specialized area of the plasma membrane called the active zone that mediates neurotransmitter release. RIM1α is a multidomain protein that constitutes a central component of the active zone by binding to other active zone proteins such as Munc13 s,α-liprins, and ELKS, and to synaptic vesicle proteins such as Rab3 and synaptotagmin-1. In mice, knockout of RIM1α significantly impairs synaptic vesicle priming and presynaptic long-term plasticity, but is not lethal. We now find that the RIM1 gene encodes a second, previously unknown RIM1 isoform called RIM1α that is upregulated in RIM1α knock-out mice. RIM1β is identical to RIM1α except for the N terminus where RIM1β lacks the N-terminal Rab3-binding sequence of RIM1α. Using newly generated knock-out mice lacking both RIM1α and RIM1β, we demonstrate that different from the deletion of only RIM1α, deletion of both RIM1α and RIM1β severely impairs mouse survival. Electrophysiological analyses show that the RIM1αβ deletion abolishes long-term presynaptic plasticity, as does RIM1α deletion alone. In contrast, the impairment in synaptic strength and short-term synaptic plasticity that is caused by the RIM1α deletion is aggravated by the deletion of both RIM1α and RIM1β. Thus, our data indicate that the RIM1 gene encodes two different isoforms that perform overlapping but distinct functions in neurotransmitter release.

Original languageEnglish (US)
Pages (from-to)13435-13447
Number of pages13
JournalJournal of Neuroscience
Volume28
Issue number50
DOIs
StatePublished - Dec 10 2008

Keywords

  • Active zone
  • Munc13
  • Neurotransmitter release
  • RIM
  • Rab3
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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