Hax1 regulates neutrophil adhesion and motility through RhoA.
Hax1 regulates neutrophil adhesion and motility through RhoA.
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DOI：
10.1083/jcb.201010143
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发表时间：
2011-05-02
期刊：
影响因子：
--
通讯作者：
Huttenlocher A
中科院分区：
文献类型：
--
作者：
Cavnar PJ;Berthier E;Beebe DJ;Huttenlocher A
Hax1的缺失与严重的先天性中性粒细胞减少综合征有关，它会损害中性粒细胞尾足分离和定向迁移。Kostmann病是一种遗传性严重先天性中性粒细胞减少综合征，与衔接蛋白hs1相关蛋白X-1 （Hax1）的功能丧失突变相关。Hax1如何调节中性粒细胞的功能在很大程度上仍然未知。在本文中，我们使用核糖核酸干扰来消耗中性粒细胞样细胞系PLB-985中的Hax1，并鉴定Hax1是整合素介导的粘附和趋化性的负调节因子。使用微流体，我们表明Hax1的消耗损害中性粒细胞尾足分离和定向迁移。hax1缺陷细胞也表现出整合素介导的粘附增加和RhoA活性降低。此外，RhoA的缺失诱导中性粒细胞粘附增加和迁移受损，表明Hax1通过RhoA调节中性粒细胞粘附和趋化性。因此，RhoA的激活足以挽救hax1缺陷中性粒细胞的粘附。总之，我们的研究结果确定Hax1是中性粒细胞尾足分离和通过RhoA趋化的新调节剂。
Loss of Hax1, which is associated with a severe congenital neutropenia syndrome, impairs neutrophil uropod detachment and directed migration. 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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影响因子：
4.8
作者：
Hao, JJ;Zhu, JW;Zhan, X
通讯作者：
Zhan, X
影响因子：
20.3
作者：
Walters, Kevin B.;Green, Julie M.;Huttenlocher, Anna
通讯作者：
Huttenlocher, Anna
影响因子：
3.3
作者：
Servant, G;Weiner, OD;Bourne, HR
通讯作者：
Bourne, HR
DOI：
10.1083/jcb.201002067
发表时间：
2010-08-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Heasman SJ;Carlin LM;Cox S;Ng T;Ridley AJ
通讯作者：
Ridley AJ
影响因子：
12.4
作者：
Jeyaraju, D. V.;Cisbani, G.;De Brito, O. M.;Koonin, E. V.;Pellegrini, L.
通讯作者：
Pellegrini, L.