Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin.
The morphogenesis of dendritic spines, the major sites of excitatory synaptic transmission in the brain, is important in synaptic development and plasticity. We have identified an ephrinB-EphB receptor trans-synaptic signaling pathway which regulates the morphogenesis and maturation of dendritic spines in hippocampal neurons. Activation of the EphB receptor induces translocation of the Rho-GEF kalirin to synapses and activation of Rac1 and its effector PAK. Overexpression of dominant-negative EphB receptor, catalytically inactive kalirin, or dominant-negative Rac1, or inhibition of PAK eliminates ephrin-induced spine development. This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity.
Penzes
Peter
P
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Beeser
Alexander
A
Chernoff
Jonathan
J
Schiller
Martin R
MR
Eipper
Betty A
BA
Mains
Richard E
RE
Huganir
Richard L
RL
D015153:Blotting, Western; D002352:Carrier Proteins; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects* / Q000648:ultrastructure; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000196:embryology*; D006801:Humans; D007202:Indicators and Reagents; D009024:Morphogenesis; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation; D036081:Receptors, Eph Family / Q000502:physiology*; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D016707:Tissue Fixation; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000502:physiology
D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D007202:Indicators and Reagents; C102365:Kalrn protein, rat; D064067:Rho Guanine Nucleotide Exchange Factors; D036081:Receptors, Eph Family; D020830:rac1 GTP-Binding Protein