A coordinated local translational control point at the synapse involving relief from silencing and MOV10 degradation

Neuron. 2009 Dec 24;64(6):871-84. doi: 10.1016/j.neuron.2009.11.023.

Abstract

Persistent changes in synaptic strength are locally regulated by both protein degradation and synthesis; however, the coordination of these opposing limbs is poorly understood. Here, we found that the RISC protein MOV10 was present at synapses and was rapidly degraded by the proteasome in an NMDA-receptor-mediated activity-dependent manner. We designed a translational trap to capture those mRNAs whose spatiotemporal translation is regulated by MOV10. When MOV10 was suppressed, a set of mRNAs--including alpha-CaMKII, Limk1, and the depalmitoylating enzyme lysophospholipase1 (Lypla1)--selectively entered the polysome compartment. We also observed that Lypla1 mRNA is associated with the brain-enriched microRNA miR-138. Using a photoconvertible translation reporter, Kaede, we analyzed the activity-dependent protein synthesis driven by Lypla1 and alpha-CaMKII 3'UTRs. We established this protein synthesis to be MOV10 and proteasome dependent. These results suggest a unifying picture of a local translational regulatory mechanism during synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Brain / metabolism*
  • Brain / ultrastructure
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cells, Cultured
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Gene Silencing / physiology*
  • Lim Kinases / metabolism
  • MicroRNAs / genetics
  • Neural Pathways / metabolism
  • Neural Pathways / ultrastructure
  • Neuronal Plasticity / genetics
  • Organ Culture Techniques
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Biosynthesis / physiology*
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Synapses / genetics
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • Synaptic Transmission / genetics
  • Thiolester Hydrolases / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN138 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Lim Kinases
  • Limk1 protein, mouse
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Mov10 protein, human
  • LYPLA1 protein, human
  • Thiolester Hydrolases
  • Proteasome Endopeptidase Complex
  • MOV10 protein, rat
  • DNA Helicases
  • RNA Helicases