Pin1 and PKMζ Sequentially Control Dendritic Protein Synthesis

Some forms of learning and memory and their electrophysiologic correlate, long-term potentiation (LTP), require dendritic translation. We demonstrate that Pin1 (protein interacting with NIMA 1), a peptidylprolyl isomerase, is present in dendritic spines and shafts and inhibits protein synthesis induced by glutamatergic signaling. Pin1 suppression increased dendritic translation, possibly through eukaryotic translation initiation factor 4E (eIF4E) and eIF4E binding proteins 1 and 2 (4E-BP1/2). Consistent with increased protein synthesis, hippocampal slices from Pin(-/-) mice had normal early LTP (E-LTP) but significantly enhanced late LTP (L-LTP) compared to wild-type controls. Protein kinase C zeta (PKC zeta) and protein kinase M zeta (PKM zeta) were increased in Pin1(-/-) mouse brain, and their activity was required to maintain dendritic translation. PKM zeta interacted with and inhibited Pin1 by phosphorylating serine 16. Therefore, glutamate-induced, dendritic protein synthesis is sequentially regulated by Pin1 and PKM zeta signaling.