Integrins control dendritic spine plasticity in hippocampal neurons through NMDA receptor and Ca2+/calmodulin-dependent protein kinase II-mediated actin reorganization.
The formation of dendritic spines during development and their structural plasticity in the adult brain are critical aspects of synaptogenesis and synaptic plasticity. Many different factors and proteins have been shown to control dendritic spine development and remodeling (Ethell and Pasquale, 2005). The extracellular matrix (ECM) components and their cell surface receptors, integrins, have been found in the vicinity of synapses and shown to regulate synaptic efficacy and play an important role in long-term potentiation (Bahr et al., 1997; Chavis and Westbrook, 2001; Chan et al., 2003; Lin et al., 2003; Bernard-Trifilo et al., 2005). Although molecular mechanisms by which integrins affect synaptic efficacy have begun to emerge, their role in structural plasticity is poorly understood. Here, we show that integrins are involved in spine remodeling in cultured hippocampal neurons. The treatment of 14 d in vitro hippocampal neurons with arginine-glycine-aspartate (RGD)-containing peptide, an established integrin ligand, induced elongation of existing dendritic spines and promoted formation of new filopodia. These effects were also accompanied by integrin-dependent actin reorganization and synapse remodeling, which were partially inhibited by function-blocking antibodies against beta1 and beta3 integrins. This actin reorganization was blocked with the NMDA receptor (NMDAR) antagonist MK801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate]. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 (N-[2-[N-(4-chlorocinnamyl)-N-methylaminomethyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide) also suppressed RGD-induced actin reorganization and synapse remodeling. Our findings show that integrins control ECM-mediated spine remodeling in hippocampal neurons through NMDAR/CaMKII-dependent actin reorganization.
Division of Biomedical Sciences, University of California Riverside, Riverside, California 92521-0121, USA.
Yang
Y
Shi
Iryna M
IM
Ethell
D000199:Actins / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*
D000199:Actins; D016023:Integrins; D009842:Oligopeptides; D016194:Receptors, N-Methyl-D-Aspartate; C047981:arginyl-glycyl-aspartic acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases