A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory.
The scaffolding protein WAVE-1 (Wiskott-Aldrich syndrome protein family member 1) directs signals from the GTPase Rac through the Arp2/3 complex to facilitate neuronal actin remodeling. The WAVE-associated GTPase activating protein called WRP is implicated in human mental retardation, and WAVE-1 knock-out mice have altered behavior. Neuronal time-lapse imaging, behavioral analyses, and electrophysiological recordings from genetically modified mice were used to show that WAVE-1 signaling complexes control aspects of neuronal morphogenesis and synaptic plasticity. Gene targeting experiments in mice demonstrate that WRP anchoring to WAVE-1 is a homeostatic mechanism that contributes to neuronal development and the fidelity of synaptic connectivity. This implies that signaling through WAVE-1 complexes is essential for neural plasticity and cognitive behavior.
Soderling
Scott H
SH
Howard Hughes Medical Institute, Oregon Health & Science University, Portland, Oregon 97239, USA. s.soderling@cellbio.duke.edu
Guire
Eric S
ES
Kaech
Stefanie
S
White
Jon
J
Zhang
Fang
F
Schutz
Kevin
K
Langeberg
Lorene K
LK
Banker
Gary
G
Raber
Jacob
J
Scott
John D
JD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D049229:Dendritic Spines / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D020690:GTPase-Activating Proteins; C516731:Srgap3 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family