DMCA
London and GOSH NHS Trust WC1 1EH
BibTeX
@MISC{Chou_londonand,
author = {Hsiu-chuan Chou and Inés M. Antón and Mark R. Holt and Claudia Curcio and Stefania Lanzardo and Austen Worth and Siobhan Burns and Adrian J. Thrasher and Gareth E. Jones and A Calle},
title = {London and GOSH NHS Trust WC1 1EH},
year = {}
}
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Abstract
The Wiskott-Aldrich Syndrome protein (WASP) is an adaptor protein that is essential for podosome formation in hematopoietic cells [1]. Given that 80 % of identified Wiskott-Aldrich Syndrome patients result from mutations in the binding site for WASP-interactingprotein (WIP) [2], we examined the possible role of WIP in the regulation of podosome architecture and cell motility in dendritic cells (DCs). Our results show that WIP is essential both for the formation of actin cores containing WASP and cortactin and for the organization of integrin and integrin-associated proteins in circular arrays, specific characteristics of podosome structure. We also found that WIP is essential for the maintenance of the high turnover of adhesions and polarity in DCs. WIP exerts these functions by regulating calpain-mediated cleavage of WASP and by facilitating the localization of WASP to sites of actin polymerization at podosomes. Taken together, our results indicate that WIP is critical for the regulation of both the stability and localization of WASP in migrating DCs and suggest that WASP and WIP operate as a functional unit to control DC motility in response to changes in the extracellular environment. Results and Discussion Cell migration requires the rearrangement of adhesions and cytoskeleton in response to extracellular stimuli to form a leading edge that allows directed locomotion. *Correspondence:
Keyphrases
gosh nh trust wc1 adaptor protein dendritic cell hematopoietic cell actin polymerization wiskott-aldrich syndrome patient high turnover calpain-mediated cleavage podosome formation actin core wiskott-aldrich syndrome protein podosome structure dc motility podosome architecture cell motility possible role specific characteristic functional unit discussion cell migration extracellular environment binding site circular array integrin-associated protein
