Different Rho GTPase-dependent signaling pathways initiate sequential steps in the consolidation of long-term potentiation.
The releasable factor adenosine blocks the formation of long-term potentiation (LTP). These experiments used this observation to uncover the synaptic processes that stabilize the potentiation effect. Brief adenosine infusion blocked stimulation-induced actin polymerization within dendritic spines along with LTP itself in control rat hippocampal slices but not in those pretreated with the actin filament stabilizer jasplakinolide. Adenosine also blocked activity-driven phosphorylation of synaptic cofilin but not of synaptic p21-activated kinase (PAK). A search for the upstream origins of these effects showed that adenosine suppressed RhoA activity but only modestly affected Rac and Cdc42. A RhoA kinase (ROCK) inhibitor reproduced adenosine's effects on cofilin phosphorylation, spine actin polymerization, and LTP, whereas a Rac inhibitor did not. However, inhibitors of Rac or PAK did prolong LTP's vulnerability to reversal by latrunculin, a toxin which blocks actin filament assembly. Thus, LTP induction initiates two synaptic signaling cascades: one (RhoA-ROCK-cofilin) leads to actin polymerization, whereas the other (Rac-PAK) stabilizes the newly formed filaments.
Rex
Christopher S
CS
Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697, USA. crex@uci.edu
Chen
Lulu Y
LY
Sharma
Anupam
A
Liu
Jihua
J
Babayan
Alex H
AH
Gall
Christine M
CM
Lynch
Gary
G
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D054462:p21-Activated Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D000199:Actins; D054462:p21-Activated Kinases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000241:Adenosine