A role for RhoB in synaptic plasticity and the regulation of neuronal morphology.
Actin-rich dendritic spines are the locus of excitatory synaptic transmission and plastic events such as long-term potentiation (LTP). Morphological plasticity of spines accompanies activity-dependent changes in synaptic strength. Several Rho GTPase family members are implicated in regulating neuronal and, in particular, spine structure via actin and the actin-binding protein cofilin. However, despite expression in hippocampus and cortex, its ability to modulate actin-regulatory proteins, and its induction during aging, RhoB has been relatively neglected. We previously demonstrated that LTP is associated with specific RhoB activation. Here, we further examined its role in synaptic function using mice with genetic deletion of the RhoB GTPase (RhoB(-/-) mice). Normal basal synaptic transmission accompanied reduced paired-pulse facilitation and post-tetanic potentiation in the hippocampus of RhoB(-/-) mice. Early phase LTP was significantly reduced in RhoB(-/-) animals, whereas the later phase was unaffected. In wild-type mice (RhoB(+/+)), Western blot analysis of potentiated hippocampus showed significant increases in phosphorylated cofilin relative to nonpotentiated slices, which were dramatically impaired in RhoB(-/-) slices. There was also a deficit in phosphorylated Lim kinase levels in the hippocampus from RhoB(-/-) mice. Morphological analysis suggested that lack of RhoB resulted in increased dendritic branching and decreased spine number. Furthermore, an increase in the proportion of stubby relative to thin spines was observed. Moreover, spines demonstrated increased length along with increased head and neck widths. These data implicate RhoB in cofilin regulation and dendritic and spine morphology, highlighting its importance in synaptic plasticity at a structural and functional level.
McNair
Kara
K
Neuroscience and Molecular Pharmacology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Spike
Rosemary
R
Guilding
Clare
C
Prendergast
George C
GC
Stone
Trevor W
TW
Cobb
Stuart R
SR
Morris
Brian J
BJ
D000818:Animals; D048430:Cell Shape / Q000235:genetics; D051338:Cofilin 1 / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D054461:Lim Kinases / Q000378:metabolism; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D020743:rhoB GTP-Binding Protein / Q000235:genetics*
C495812:Cfl1 protein, rat; D051338:Cofilin 1; D054461:Lim Kinases; D020743:rhoB GTP-Binding Protein