Convergent CaMK and RacGEF signals control dendritic structure and function.
Structural plasticity of excitatory synapses is a vital component of neuronal development, synaptic plasticity and behavior, and its malfunction underlies many neurodevelopmental and psychiatric disorders. However, the molecular mechanisms that control dendritic spine morphogenesis have only recently emerged. We summarize recent work that has revealed an important connection between calcium/calmodulin-dependent kinases (CaMKs) and guanine-nucleotide-exchange factors (GEFs) that activate the small GTPase Rac (RacGEFs) in controlling dendritic spine morphogenesis. These two groups of molecules function in neurons as a unique signaling cassette that transduces calcium influx into small GTPase activity and, thence, actin reorganization and spine morphogenesis. Through this pathway, CaMKs and RacGEFs amplify calcium signals and translate them into spatially and temporally regulated structural remodeling of dendritic spines.
Penzes
Peter
P
Department of Physiology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA. p-penzes@northwestern.edu
Cahill
Michael E
ME
Jones
Kelly A
KA
Srivastava
Deepak P
DP
D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure*; D049229:Dendritic Spines / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020744:rac GTP-Binding Proteins; D002118:Calcium