AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade.
AMPA receptors (AMPA-R) are major mediators of synaptic transmission and plasticity in the developing and adult central nervous system. Activity-dependent structural plasticity mediated by dynamic changes in the morphology of spines and dendrites is also essential for the formation and tuning of neuronal circuits. RhoA and Rac1 are known to play important roles in the regulation of spine and dendrite development in response to neuronal activity. These Rho GTPases are activated by guanine nucleotide exchange factors (GEFs). In this study, we identified GEF-H1/Lfc as a component of the AMPA-R complex in the brain. GEF-H1 is enriched in the postsynaptic density and is colocalized with GluR1 at spines. GEF-H1 activity negatively regulates spine density and length through a RhoA signaling cascade. In addition, AMPA-R-dependent changes in spine development are eliminated by down-regulation of GEF-H1. Altogether, these results strongly suggest that GEF-H1 is an important mediator of AMPA-R activity-dependent structural plasticity in neurons.
Kang
Myoung-Goo
MG
Department of Neuroscience, The Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Guo
Yurong
Y
Huganir
Richard L
RL
D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism*; D015536:Down-Regulation; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
C000609216:Arhgef2 protein, rat; D018091:Receptors, AMPA; D064067:Rho Guanine Nucleotide Exchange Factors; D020742:rhoA GTP-Binding Protein