title: Pin1 and PKMzeta sequentially control dendritic protein synthesis.
abstract: 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 peptidyl-prolyl 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 (PKCzeta) and protein kinase M zeta (PKMzeta) were increased in Pin1(-/-) mouse brain, and their activity was required to maintain dendritic translation. PKMzeta interacted with and inhibited Pin1 by phosphorylating serine 16. Therefore, glutamate-induced, dendritic protein synthesis is sequentially regulated by Pin1 and PKMzeta signaling.
authors.affiliation: Department of Pathology and Laboratory Medicine and Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Westmark
authors.forename: Cara J
authors.initials: CJ
authors.lastname: Westmark
authors.forename: SuQing
authors.initials: S
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Levenson
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Riordan
authors.forename: Corinna
authors.initials: C
authors.lastname: Burger
authors.forename: James S
authors.initials: JS
authors.lastname: Malter
mesh_terms: D000818:Animals; D055162:Biocatalysis; D003712:Dendrites / Q000378:metabolism*; D017774:Long-Term Potentiation; D051379:Mice; D008822:Mice, Transgenic; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D019696:Peptidylprolyl Isomerase / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D000099221:Protein Kinase C zeta
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009419:Nerve Tissue Proteins; D019696:Peptidylprolyl Isomerase; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta; C000606850:Pin1 protein, mouse