title: A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Oregon Health & Science University, Portland, Oregon 97239, USA. s.soderling@cellbio.duke.edu
authors.forename: Scott H
authors.initials: SH
authors.lastname: Soderling
authors.forename: Eric S
authors.initials: ES
authors.lastname: Guire
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kaech
authors.forename: Jon
authors.initials: J
authors.lastname: White
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.forename: Kevin
authors.initials: K
authors.lastname: Schutz
authors.forename: Lorene K
authors.initials: LK
authors.lastname: Langeberg
authors.forename: Gary
authors.initials: G
authors.lastname: Banker
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: John D
authors.initials: JD
authors.lastname: Scott
mesh_terms: 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*
chemical_list: D020690:GTPase-Activating Proteins; C516731:Srgap3 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family