Abstract
The WAVE-associated Rac GAP, WRP, is thought to regulate key aspects of synapse development and function and may be linked to mental retardation in humans. WRP contains a newly described inverse F-BAR (IF-BAR) domain of unknown function. Our studies show that this domain senses/facilitates outward protrusions analogous to filopodia and that the molecular basis for this is likely explained by a convex lipid-binding surface on the WRP IF-BAR domain. In dendrites the IF-BAR domain of WRP forms a bud on the shaft from which precursors to spines emerge. Loss of WRP in vivo and in vitro results in reduced density of spines. In vivo this is primarily a loss of mushroom-shaped spines. Developmentally, WRP function is critical at the onset of spinogenesis, when dendritic filopodia are prevalent. Finally, because WRP is implicated in mental retardation, behaviors of WRP heterozygous and null mice have been evaluated. Results from these studies confirm that loss of WRP is linked to impaired learning and memory.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Avoidance Learning
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Cells, Cultured
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Chlorocebus aethiops
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Dendritic Spines / physiology*
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Dendritic Spines / ultrastructure
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Disease Models, Animal
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Electroshock / methods
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GTPase-Activating Proteins / chemistry*
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GTPase-Activating Proteins / deficiency
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GTPase-Activating Proteins / metabolism*
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Green Fluorescent Proteins / genetics
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Hippocampus / cytology
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Humans
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Lipid Metabolism / genetics
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Liposomes / metabolism
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Maze Learning
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Memory Disorders / genetics
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Memory Disorders / metabolism*
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Mice
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Mice, Knockout
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Microscopy, Electron, Scanning / methods
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Models, Chemical
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Neurons / metabolism
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Neurons / ultrastructure*
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Neuropsychological Tests
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Phosphatidylinositols / metabolism
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Protein Interaction Domains and Motifs / genetics
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Protein Interaction Domains and Motifs / physiology*
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Sensation / genetics
Substances
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GTPase-Activating Proteins
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Liposomes
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Phosphatidylinositols
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Srgap3 protein, mouse
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Green Fluorescent Proteins