Pin1 and PKMζ Sequentially Control Dendritic Protein Synthesis

Sci. Signal., 9 March 2010
Vol. 3, Issue 112, p. ra18
DOI: 10.1126/scisignal.2000451

Pin1 and PKMζ Sequentially Control Dendritic Protein Synthesis

  1. Pamela R. Westmark1,
  2. Cara J. Westmark1,
  3. SuQing Wang1,*,
  4. Jonathan Levenson2,
  5. Kenneth J. O’Riordan3,
  6. Corinna Burger3, and
  7. James S. Malter1,
  1. 1Department of Pathology and Laboratory Medicine and Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI 53705, USA.
  2. 2Galenea Inc., 300 Technology Square, Cambridge, MA 02139, USA.
  3. 3Department of Neurology, University of Wisconsin, Madison, WI 53705, USA.
  1. To whom correspondence should be addressed. E-mail: jsmalter{at}wisc.edu
  • * 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 ζ (PKCζ) and protein kinase M ζ (PKMζ) were increased in Pin1−/− mouse brain, and their activity was required to maintain dendritic translation. PKMζ interacted with and inhibited Pin1 by phosphorylating serine 16. Therefore, glutamate-induced, dendritic protein synthesis is sequentially regulated by Pin1 and PKMζ signaling.

Citation:

P. R. Westmark, C. J. Westmark, S. Wang, J. Levenson, K. J. O’Riordan, C. Burger, and J. S. Malter, Pin1 and PKMζ Sequentially Control Dendritic Protein Synthesis. Sci. Signal. 3, ra18 (2010).

GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories
O. Hardt, K. Nader, and Y.-T. Wang
Phil Trans R Soc B 369, 20130141-20130141 (2 December 2013)

Cellular and subcellular localization of PKM{zeta}
A. I. Hernandez, W. C. Oxberry, J. F. Crary, S. S. Mirra, and T. C. Sacktor
Phil Trans R Soc B 369, 20130140-20130140 (2 December 2013)

Pin1-FADD Interactions Regulate Fas-Mediated Apoptosis in Activated Eosinophils
J. Oh, and J. S. Malter
J. Immunol. 190, 4937-4945 (15 May 2013)

Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function
V. Rangasamy, R. Mishra, G. Sondarva, S. Das, T. H. Lee, J. C. Bakowska, G. Tzivion, J. S. Malter, B. Rana, K. P. Lu et al.
Proc. Natl. Acad. Sci. USA 109, 8149-8154 (22 May 2012)

A late phase of LTD in cultured cerebellar Purkinje cells requires persistent dynamin-mediated endocytosis
D. J. Linden, R. Mishra, G. Sondarva, S. Das, T. H. Lee, J. C. Bakowska, G. Tzivion, J. S. Malter, B. Rana, K. P. Lu et al.
J. Neurophysiol. 107, 448-454 (1 January 2012)

PINing for Things Past
T. C. Sacktor, R. Mishra, G. Sondarva, S. Das, T. H. Lee, J. C. Bakowska, G. Tzivion, J. S. Malter, B. Rana, K. P. Lu et al.
Sci Signal 3, pe9-pe9 (9 March 2010)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882