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Journal article
Hax1 regulates neutrophil adhesion and motility through RhoA
The Journal of cell biology, Vol.193(3), pp.465-473
05/02/2011
PMCID: PMC3087009
PMID: 21518791
Web of Science ID: WOS:000290676400007
Abstract
Kostmann disease is an inherited severe congenital neutropenia syndrome associated with loss-of-function mutations in an adaptor protein HS1-associated protein X-1 (Hax1). How Hax1 regulates neutrophil function remains largely unknown. In this paper, we use ribonucleic acid interference to deplete Hax1 in the neutrophil-like cell line PLB-985 and identify Hax1 as a negative regulator of integrin-mediated adhesion and chemotaxis. Using microfluidics, we show that depletion of Hax1 impairs neutrophil uropod detachment and directed migration. Hax1-deficient cells also display increased integrin-mediated adhesion and reduced RhoA activity. Moreover, depletion of RhoA induces increased neutrophil adhesion and impaired migration, suggesting that Hax1 regulates neutrophil adhesion and chemotaxis through RhoA. Accordingly, activation of RhoA is sufficient to rescue adhesion of Hax1-deficient neutrophils. Together, our findings identify Hax1 as a novel regulator of neutrophil uropod detachment and chemotaxis through RhoA.
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- Title
- Hax1 regulates neutrophil adhesion and motility through RhoA
- Publication Details
- The Journal of cell biology, Vol.193(3), pp.465-473
- Resource Type
- Journal article
- Publisher
- Rockefeller Univ Press
- Format
- pdf
- Number of pages
- 9
- Grant note
- T32ES007015 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) R01GM074827 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) T32ES007015; GM074827 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Burroughs Wellcome grant; Burroughs Wellcome Fund 10POST3230031 / American Heart Association R01EB010039 / NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)
- Copyright
- © 2011 Cavnar et al. This article is distributed under the terms of an AttributionNoncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
- Identifiers
- WOS:000290676400007; 99380171296106600
- Academic Unit
- Biology; Hal Marcus College of Science and Engineering
- Language
- English