Phosphorylation of RIM1alpha by PKA triggers presynaptic long-term potentiation at cerebellar parallel fiber synapses.
Presynaptic activation of protein kinase A (PKA) induces LTP in cerebellar parallel fiber synapses. Presynaptic LTP is known to require the active zone protein RIM1alpha, but the underlying induction mechanism remains unclear. We now show that PKA directly phosphorylates RIM1alpha at two sites. Using paired recordings from cultured cerebellar granule and Purkinje neurons, we demonstrate that LTP is absent in neurons from RIM1alpha KO mice but is rescued by presynaptic expression of RIM1alpha. Mutant RIM1alpha lacking the N-terminal phosphorylation site is unable to rescue LTP in RIM1alpha knockout neurons but selectively suppresses LTP in wild-type neurons. Our findings suggest that PKA-mediated phosphorylation of the active zone protein RIM1alpha at a single N-terminal site induces presynaptic LTP.
Lonart
György
G
Center for Basic Neuroscience, Department of Molecular Genetics and Howard Hughes Medical Institute, UT Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Schoch
Susanne
S
Kaeser
Pascal S
PS
Larkin
C Jenny
CJ
Südhof
Thomas C
TC
Linden
David J
DJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004594:Electrophysiology; D019204:GTP-Binding Proteins; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014162:Transfection
D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C107293:Rim protein, mammalian; C491490:Rims1 protein, mouse; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases