Neuronal structures called dendritic spines are sites of excitatory synapses, where nerve cells communicate with each other. The formation and remodeling of spines are essential for learning and memory, and abnormalities in spine formation or structure are associated with neurological and intellectual disorders.
Donna Webb, Ph.D., and colleagues explored a role for the protein Asef2, which is expressed in various regions of the mammalian brain, in spine formation. They report in the April 17 Journal of Biological Chemistry that Asef2, which activates the protein Rac, promotes dendritic spine and synapse formation. Knocking down Asef2 in neurons impairs spine and synapse formation, while overexpressing the protein increases spine and synapse density. They show that the actin-binding protein spinophilin recruits Asef2 to spines, and that this localization depends on excitatory neuronal activity.
The findings point to spinophilin-Asef2-Rac signaling as a novel mechanism for the development of dendritic spines and synapses, which is critical for maintaining normal cognitive and behavioral function.
This research was supported by the National Institutes of Health (grants GM092914, MH071674, RR025524).
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