Transient decrease in F-actin may be necessary for translocation of proteins into dendritic spines.
It remains poorly understood as to how newly synthesized proteins that are required to act at specific synapses are translocated into only selected subsets of potentiated dendritic spines. Here, we report that F-actin, a major component of the skeletal structure of dendritic spines, may contribute to the regulation of synaptic specificity of protein translocation. We found that the stabilization of F-actin blocked the translocation of GFP-CaMKII and inhibited the diffusion of 3-kDa dextran into spines (in 2-3 weeks cultures). Neuronal activation in hippocampal slices and cultured neurons led to an increase in the activation (decrease in the phosphorylation) of the actin depolymerization factor, cofilin, and a decrease in F-actin. Furthermore, the induction of long-term potentiation by tetanic stimulation induced local transient depolymerization of F-actin both in vivo and in hippocampal slices (8-10 weeks), and this local F-actin depolymerization was blocked by APV, a N-methyl-D-aspartate (NMDA) receptor antagonist. These results suggest that F-actin may play a role in synaptic specificity by allowing protein translocation into only potentiated spines, gated through its depolymerization, which is probably triggered by the activation of NMDA receptors.
Ouyang
Yannan
Y
Department of Neurology 8111, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA. ouyangy@neuro.wustl.edu
Wong
Michael
M
Capani
Francisco
F
Rensing
Nick
N
Lee
Chul-Sang
CS
Liu
Qun
Q
Neusch
Clemens
C
Martone
Maryann E
ME
Wu
Jane Y
JY
Yamada
Kelvin
K
Ellisman
Mark H
MH
Choi
Dennis W
DW
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D047630:Depsipeptides / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005455:Fluorescent Antibody Technique / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008565:Membrane Proteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011189:Potassium Chloride / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013997:Time Factors; D014162:Transfection
D051339:Actin Depolymerizing Factors; D000199:Actins; D047630:Depsipeptides; D003911:Dextrans; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C489787:MAP2 protein, rat; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C057531:jasplakinolide; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride; D015763:2-Amino-5-phosphonovalerate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases