Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines.
Activity-dependent rapid structural and functional modifications of central excitatory synapses contribute to synapse maturation, experience-dependent plasticity, and learning and memory and are associated with neurodevelopmental and psychiatric disorders. However, the signal transduction mechanisms that link glutamate receptor activation to intracellular effectors that accomplish structural and functional plasticity are not well understood. Here we report that NMDA receptor activation in pyramidal neurons causes CaMKII-dependent phosphorylation of the guanine-nucleotide exchange factor (GEF) kalirin-7 at residue threonine 95, regulating its GEF activity, leading to activation of small GTPase Rac1 and rapid enlargement of existing spines. Kalirin-7 also interacts with AMPA receptors and controls their synaptic expression. By demonstrating that kalirin expression and spine localization are required for activity-dependent spine enlargement and enhancement of AMPAR-mediated synaptic transmission, our study identifies a signaling pathway that controls structural and functional spine plasticity.
Xie
Zhong
Z
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Srivastava
Deepak P
DP
Photowala
Huzefa
H
Kai
Li
L
Cahill
Michael E
ME
Woolfrey
Kevin M
KM
Shum
Cassandra Y
CY
Surmeier
D James
DJ
Penzes
Peter
P
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D018091:Receptors, AMPA / Q000819:agonists / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D013912:Threonine / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D020662:Guanine Nucleotide Exchange Factors; C102365:Kalrn protein, rat; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013912:Threonine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020830:rac1 GTP-Binding Protein