WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Carlson, BR; Lloyd, KE; Kruszewski, A; Kim, I-H; Rodriguiz, RM; Heindel, C; Faytell, M; Dudek, SM; Wetsel, WC; Soderling, SH

Published Date

  • February 16, 2011

Published In

Volume / Issue

  • 31 / 7

Start / End Page

  • 2447 - 2460

PubMed ID

  • 21325512

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.4433-10.2011

Language

  • eng

Conference Location

  • United States