AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade

Myoung Goo Kang, Yurong Guo, Richard L. Huganir

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3549-3554
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number9
DOIs
StatePublished - Mar 3 2009

Keywords

  • GTPase
  • Glutamate receptor
  • Learning and memory
  • Structural plasticity
  • Synaptic plasticity

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade'. Together they form a unique fingerprint.

  • Cite this