Pin1 and PKM
Sequentially Control Dendritic Protein Synthesis
Pamela R. Westmark1,
Cara J. Westmark1,
SuQing Wang1*,
Jonathan Levenson2,
Kenneth J. O’Riordan3,
Corinna Burger3, and
James S. Malter1
1 Department of Pathology and Laboratory Medicine and Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI 53705, USA.
2 Galenea Inc., 300 Technology Square, Cambridge, MA 02139, USA.
3 Department of Neurology, University of Wisconsin, Madison, WI 53705, USA.
* Present address: Department of Nutrition and Food Health, School of Public Health, Wuhan University, 430071 P.R. China.
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 
(PKC) and protein kinase M (PKM) were increased in Pin1–/– mouse brain, and their activity was required to maintain dendritic translation. PKM interacted with and inhibited Pin1 by phosphorylating serine 16. Therefore, glutamate-induced, dendritic protein synthesis is sequentially regulated by Pin1 and PKM signaling.
To whom correspondence should be addressed. E-mail: jsmalter{at}wisc.edu
