Actin polymerization regulates the synthesis of PKMzeta in LTP.
Changes in the actin-based synaptic cytoskeleton are important for long-term potentiation (LTP), but the mechanism linking actin filament formation and the persistence of enhanced synaptic transmission has not been described. Actin filaments form rapidly during LTP induction without new protein synthesis, but their effects on synaptic potentiation occur during protein synthesis-dependent late-LTP. Previous studies have shown that late-LTP is mediated by the synthesis of the persistently active, atypical PKC isoform, protein kinase Mzeta (PKMzeta). Here we show that preventing actin polymerization during LTP with latrunculin B blocks de novo protein synthesis of PKMzeta. In contrast, the agent has minimal effects on the potentiation of AMPA receptors mediated by postsynaptically perfused PKMzeta or on LTP expression. Thus actin filaments formed by tetanization enhance the efficiency of the synthesis of PKMzeta that maintains LTP.
Kelly
Matthew Taylor
MT
Department of Physiology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203, USA.
Yao
Yudong
Y
Sondhi
Rachna
R
Sacktor
Todd Charlton
TC
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000502:physiology; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D018408:Patch-Clamp Techniques / Q000379:methods; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D053778:Thiazolidines / Q000494:pharmacology
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D053778:Thiazolidines; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat; C037068:latrunculin B