期刊
JOURNAL OF NEUROSCIENCE
卷 31, 期 7, 页码 2447-2460出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4433-10.2011
关键词
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资金
- National Institutes of Health [R01-NS059957]
- March of Dimes Grant Basil O'Connor Starter Scholar Research Grant [5-FY07-671]
- Dana Foundation
- National Institute of Environmental Health Sciences [1ZIAES100221-08]
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.
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