p120 catenin regulates dendritic spine and synapse development through Rho-family GTPases and cadherins.
Both the cadherin-catenin complex and Rho-family GTPases have been shown to regulate dendrite development. We show here a role for p120 catenin (p120ctn) in regulating spine and synapse formation in the developing mouse brain. p120catenin gene deletion in hippocampal pyramidal neurons in vivo resulted in reduced spine and synapse densities along dendrites. In addition, p120 catenin loss resulted in reduced cadherin levels and misregulation of Rho-family GTPases, with decreased Rac1 and increased RhoA activity. Analyses in vitro indicate that the reduced spine density reflects aberrant Rho-family GTPase signaling, whereas the effects on spine maturation appear to result from reduced cadherin levels and possibly aberrant Rho-family GTPase signaling. Thus, p120ctn acts as a signal coordinator between cadherins and Rho-family GTPases to regulate cytoskeletal changes required during spine and synapse development.
Elia
Lisa P
LP
Howard Hughes Medical Institute and Department of Physiology, 1550 Fourth Street, University of California, San Francisco, San Francisco, California 94143, USA.
Yamamoto
Miya
M
Zang
Keling
K
Reichardt
Louis F
LF
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D015536:Down-Regulation / Q000235:genetics; D017353:Gene Deletion; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse