A coordinated local translational control point at the synapse involving relief from silencing and MOV10 degradation.
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.
Banerjee
Sourav
S
Neuroscience Research Institute and Department of Cellular Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Neveu
Pierre
P
Kosik
Kenneth S
KS
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing / Q000502:physiology*; D054461:Lim Kinases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D009434:Neural Pathways / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000235:genetics; D009924:Organ Culture Techniques; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D013869:Thiolester Hydrolases / Q000378:metabolism
D020413:3' Untranslated Regions; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C530476:Mov10 protein, human; C402226:LYPLA1 protein, human; D013869:Thiolester Hydrolases; D046988:Proteasome Endopeptidase Complex; C547194:MOV10 protein, rat; D004265:DNA Helicases; D020365:RNA Helicases