Adapter protein 14-3-3 is required for a presynaptic form of LTP in the cerebellum.

Long-term potentiation (LTP) of granule cell-Purkinje cell synapses in the mouse cerebellum requires phosphorylation by protein kinase A of the active-zone protein RIM1alpha at Ser413. Here, we show that the adapter protein 14-3-3 readily binds phosphorylated Ser413 in RIM1alpha, and that presynaptic transfection with a dominant-negative 14-3-3eta mutant, or a RIM1alpha mutant with enhanced 14-3-3 binding, inhibits LTP. Thus, RIM1alpha phosphorylation triggers presynaptic LTP in part through recruitment of 14-3-3 to phospho-Ser413-RIM1alpha.