Actin polymerization and ERK phosphorylation are required for Arc/Arg3.1 mRNA targeting to activated synaptic sites on dendrites.
The mRNA for the immediate early gene Arc/Arg3.1 is induced by strong synaptic activation and is rapidly transported into dendrites, where it localizes at active synaptic sites. NMDA receptor activation is critical for mRNA localization at active synapses, but downstream events that mediate localization are not known. The patterns of synaptic activity that induce mRNA localization also trigger a dramatic polymerization of actin in the activated dendritic lamina and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) throughout the postsynaptic cytoplasm. The local polymerization of actin in the activated dendritic lamina is of particular interest because it occurs in the same dendritic domains in which newly synthesized Arc/Arg3.1 mRNA localizes. Here, we explore the role of activity-induced alterations in the actin network and mitogen-activated protein (MAP) kinase activation in Arc/Arg3.1 mRNA localization. We show that actin polymerization induced by high-frequency stimulation is blocked by local inhibition of Rho kinase, and Arc/Arg3.1 mRNA localization is abrogated in the region of Rho kinase blockade. Local application of latrunculin B, which binds to actin monomers and inhibits actin polymerization, also blocked the targeting of Arc/Arg3.1 mRNA to activated synaptic sites. Local application of the MAP kinase kinase inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio]butadiene) blocked ERK phosphorylation, and also blocked Arc/Arg3.1 mRNA localization. Our results indicate that the reorganization of the actin cytoskeletal network in conjunction with MAP kinase activation is required for targeting newly synthesized Arc/Arg3.1 mRNA to activated synaptic sites.
Huang
Fen
F
Department of Anatomy and Neurobiology, Reeve-Irvine Research Center, Irvine, California 92697, USA.
Chotiner
Jennifer K
JK
Steward
Oswald
O
D000199:Actins / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology; D009570:Nitriles / Q000494:pharmacology; D019580:Perforant Pathway / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D053778:Thiazolidines / Q000494:pharmacology
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002070:Butadienes; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D009570:Nitriles; D012333:RNA, Messenger; D053778:Thiazolidines; C113580:U 0126; C092069:activity regulated cytoskeletal-associated protein; D048049:Extracellular Signal-Regulated MAP Kinases; C037068:latrunculin B
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