Phosphorylation of RIM1α by PKA Triggers Presynaptic Long-Term Potentiation at Cerebellar Parallel Fiber Synapses
Copyright policy )Phosphorylation of RIM1α 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.
- The University of Texas Southwestern Medical Center United States
- Johns Hopkins University School of Medicine United States
- Johns Hopkins Medicine United States
- Howard Hughes Medical Institute United States
- Eastern Virginia Medical School United States
Mice, Knockout, Neurons, Biochemistry, Genetics and Molecular Biology(all), Recombinant Fusion Proteins, Long-Term Potentiation, Molecular Sequence Data, Presynaptic Terminals, Nerve Tissue Proteins, Cyclic AMP-Dependent Protein Kinases, Electrophysiology, Mice, GTP-Binding Proteins, Cerebellum, Synapses, Serine, Animals, Amino Acid Sequence, Phosphorylation, Sequence Alignment, Cells, Cultured, Adenylyl Cyclases
Mice, Knockout, Neurons, Biochemistry, Genetics and Molecular Biology(all), Recombinant Fusion Proteins, Long-Term Potentiation, Molecular Sequence Data, Presynaptic Terminals, Nerve Tissue Proteins, Cyclic AMP-Dependent Protein Kinases, Electrophysiology, Mice, GTP-Binding Proteins, Cerebellum, Synapses, Serine, Animals, Amino Acid Sequence, Phosphorylation, Sequence Alignment, Cells, Cultured, Adenylyl Cyclases
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