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RIM1[alpha] phosphorylation at serine-413 by protein kinase A is not required for presynaptic long-term plasticity or learning
- Source :
- Proceedings of the National Academy of Sciences of the United States. Sept 23, 2008, Vol. 105 Issue 38, p14680, 6 p.
- Publication Year :
- 2008
-
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. RIM1[alpha], 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 RIM1[alpha] 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 RIM1[alpha] KO mice, RIM1 knockin mice containing the serine-413 substitution exhibit normal learning capabilities. The lack of an effect of the serine-413 mutation of RIM1[alpha] is not due to compensation by RIM2[alpha] because mice carrying both the serine-413 substitution and a RIM2[alpha] deletion still exhibited normal long-term presynaptic plasticity. Thus, phosphorylation of serine-413 of RIM1[alpha] 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 RIM1[alpha]. active zone | neurotransmitter release | Rab3 | synaptic vesicle | mossy fiber
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 105
- Issue :
- 38
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.186688373