Regulation of dendritic spine motility and stability by Rac1 and Rho kinase: evidence for two forms of spine motility.
Dendritic spines are major sites of excitatory synapses in the brain and display rapid motility, which is believed to be important for synapse formation and plasticity. Spine morphology was previously shown to be regulated by the Rho GTPases Rac1 and RhoA. Here, we analyzed the roles of Rac1 and a downstream effector of RhoA, Rho kinase, in controlling spine morphogenesis and their effects on spine motility and stability. Blockade of Rac1 induced long, thin spines and inhibited spine head growth, morphing, and stability. Spine head growth was more severely affected in mature spines. On the other hand, inhibition of Rho kinase induced new, long spines and protrusive motility. These data demonstrate that Rac1 and RhoA/Rho kinase pathways regulate different aspects of spine morphology, motility, and stability and presumably also different aspects of synaptic functions. Moreover, our data show that there are two different types of spine motility: protrusive motility and head morphing, which are differentially regulated by Rac1 and Rho kinase. We propose that these two different types of spine motility serve different functions in synaptogenesis and synapse maturation.
Tashiro
Ayumu
A
Department of Biological Sciences, Columbia University, New York, NY 10027, USA. tashiro@salk.edu
Yuste
Rafael
R
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D003712:Dendrites / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; C107953:RAC1 protein, human; C484602:Rac1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein