RIM1alpha phosphorylation at serine-413 by protein kinase A is not required for presynaptic long-term plasticity or learning.
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. RIM1alpha, 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 RIM1alpha 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 RIM1alpha 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 RIM1alpha is not due to compensation by RIM2alpha because mice carrying both the serine-413 substitution and a RIM2alpha deletion still exhibited normal long-term presynaptic plasticity. Thus, phosphorylation of serine-413 of RIM1alpha 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 RIM1alpha.
Kaeser
Pascal S
PS
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Kwon
Hyung-Bae
HB
Blundell
Jacqueline
J
Chevaleyre
Vivien
V
Morishita
Wade
W
Malenka
Robert C
RC
Powell
Craig M
CM
Castillo
Pablo E
PE
Südhof
Thomas C
TC
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001665:Binding Sites; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009412:Nerve Fibers / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000201:enzymology*; D017966:Pyramidal Cells / Q000502:physiology
D048948:14-3-3 Proteins; C491490:Rims1 protein, mouse; D010768:Phosphoserine; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins
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