RIM1α phosphorylation at serine-413 by protein kinase A is not required for presynaptic long-term plasticity or learning

Pascal S. Kaeser, Hyung Bae Kwon, Jacqueline Blundell, Vivien Chevaleyre, Wade Morishita, Robert C. Malenka, Craig M. Powell, Pablo E. Castillo, Thomas C. Südhof

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Activation of presynaptic cAMP-dependent protein kinase A (PKA) triggers presynaptic long-term plasticity in synapses such as cerebellar parallel fiber and hippocampal mossy fiber synapses. RIM1α, a large multidomain protein that forms a scaffold at the presynaptic active zone, is essential for presynaptic long-term plasticity in these synapses and is phosphorylated by PKA at serine-413. Previous studies suggested that phosphorylation of RIM1α at serine-413 is required for presynaptic long-term potentiation in parallel fiber synapses formed in vitro by cultured cerebellar neurons and that this type of presynaptic long-term potentiation is mediated by binding of 14-3-3 proteins to phosphorylated serine-413. To test the role of serine-413 phosphorylation in vivo, we have now produced knockin mice in which serine-413 is mutated to alanine. Surprisingly, we find that in these mutant mice, three different forms of presynaptic PKA-dependent long-term plasticity are normal. Furthermore, we observed that in contrast to RIM1αKO mice, RIM1 knockin mice containing the serine-413 substitution exhibit normal learning capabilities. The lack of an effect of the serine-413 mutation of RIM1α is not due to compensation by RIM2α because mice carrying both the serine-413 substitution and a RIM2α deletion still exhibited normal long-term presynaptic plasticity. Thus, phosphorylation of serine-413 of RIM1α is not essential for PKA-dependent long-term presynaptic plasticity in vivo, suggesting that PKA operates by a different mechanism despite the dependence of long-term presynaptic plasticity on RIM1α.

Original languageEnglish (US)
Pages (from-to)14680-14685
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number38
DOIs
StatePublished - Sep 23 2008

Keywords

  • Active zone
  • Mossy fiber
  • Neurotransmitter release
  • Rab3
  • Synaptic vesicle

ASJC Scopus subject areas

  • General

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