Phosphorylation of RIM1α by PKA Triggers Presynaptic Long-Term Potentiation at Cerebellar Parallel Fiber Synapses

AbstractPresynaptic activation of protein kinase A (PKA) induces LTP in cerebellar parallel fiber synapses. Presynaptic LTP is known to require the active zone protein RIM1α, but the underlying induction mechanism remains unclear. We now show that PKA directly phosphorylates RIM1α at two sites. Using paired recordings from cultured cerebellar granule and Purkinje neurons, we demonstrate that LTP is absent in neurons from RIM1α KO mice but is rescued by presynaptic expression of RIM1α. Mutant RIM1α lacking the N-terminal phosphorylation site is unable to rescue LTP in RIM1α knockout neurons but selectively suppresses LTP in wild-type neurons. Our findings suggest that PKA-mediated phosphorylation of the active zone protein RIM1α at a single N-terminal site induces presynaptic LTP