NHERF1 regulates gp120-induced internalization and signaling by CCR5, and HIV-1 production

	NHERF1 regulates gp120-induced internalization and signaling by CCR5, and HIV-1 production
	Kuang YQ 1; Pang W 2; Zheng YT 2; Dupre DJ*1; denis.dupre@dal.ca
	2012
发表期刊	EUROPEAN JOURNAL OF IMMUNOLOGY
卷号	42 期号:2 页码:299-310
合作性质	其它
摘要	The scaffolding protein Na+/H+ exchanger regulator factor 1 (NHERF1) plays an important role in the trafficking of G protein-coupled receptors. We previously demonstrated that NHERF1 is involved in chemokine receptor CCR5 homodimer internalization and signal transduction. Given the importance of CCR5 internalization during HIV-1 infection, we evaluated NHERF1's contribution in HIV-1 infection. We challenged human osteosarcoma cells coexpressing CD4 and CCR5 cells expressing either NHERF1 fragment domains or WT NHERF1 with an HIV-1 strain to examine the effects of NHERF1 on HIV-1 entry and replication. WT NHERF1 potentiates HIV-1 envelope gp120-induced CCR5 internalization, and promotes the replication of HIV-1. In order to better understand how NHERF1 affects signal transduction, different domains of NHERF1 were overexpressed in cells to analyze their effect on the different signaling pathways. Here, we show that NHERF1 can associate with CCR5, and promote activation of the gp120-induced MAPK/ERK, focal adhesion kinase and RhoA (Ras homolog gene family member A) signaling pathways. NHERF1 overexpression also increases HIV-1 host cell migration triggered by gp120 via focal adhesion kinase (FAK) signaling. Finally, NHERF1 enhanced actin filament rearrangement in host cells, an important step in post-entry HIV-1 replication events. While postsynaptic density 95/disk-large/zonula occludens 2 (PDZ2) appears to be the major contributor in those events, other domains also participate in the regulation of gp120-induced signaling pathways. Altogether, our results suggest a very important role of the scaffold NHERF1 in the regulation of HIV-1 entry and replication.
关键词	Ccr5 Gp120 g Protein-coupled Receptor h Plus Exchanger Regulator Factor 1 (Nherf1) Signaling
资助者	This work was partially supported by grants from the Canadian Institutes of Health Research (No. HOP-86863) and NSERC (No. RGPIN/355310-2008) to D.J.D. D.J.D. is the recipient of a CIHR New Investigator Award and Dalhousie Medical Research Foundation New Investigator Award. This work was also partially supported by grants from National Basical Research Program of China (No.2009CB522306), Eleven Five-Year Key Scientific and Technological Program of China (No. 2009ZX09501-029, 2008ZX10001-015, 2008ZX10005-002), and National Natural Science Fundation of China (No. U0832601) to Y.T.Z. ; This work was partially supported by grants from the Canadian Institutes of Health Research (No. HOP-86863) and NSERC (No. RGPIN/355310-2008) to D.J.D. D.J.D. is the recipient of a CIHR New Investigator Award and Dalhousie Medical Research Foundation New Investigator Award. This work was also partially supported by grants from National Basical Research Program of China (No.2009CB522306), Eleven Five-Year Key Scientific and Technological Program of China (No. 2009ZX09501-029, 2008ZX10001-015, 2008ZX10005-002), and National Natural Science Fundation of China (No. U0832601) to Y.T.Z. ; This work was partially supported by grants from the Canadian Institutes of Health Research (No. HOP-86863) and NSERC (No. RGPIN/355310-2008) to D.J.D. D.J.D. is the recipient of a CIHR New Investigator Award and Dalhousie Medical Research Foundation New Investigator Award. This work was also partially supported by grants from National Basical Research Program of China (No.2009CB522306), Eleven Five-Year Key Scientific and Technological Program of China (No. 2009ZX09501-029, 2008ZX10001-015, 2008ZX10005-002), and National Natural Science Fundation of China (No. U0832601) to Y.T.Z. ; This work was partially supported by grants from the Canadian Institutes of Health Research (No. HOP-86863) and NSERC (No. RGPIN/355310-2008) to D.J.D. D.J.D. is the recipient of a CIHR New Investigator Award and Dalhousie Medical Research Foundation New Investigator Award. This work was also partially supported by grants from National Basical Research Program of China (No.2009CB522306), Eleven Five-Year Key Scientific and Technological Program of China (No. 2009ZX09501-029, 2008ZX10001-015, 2008ZX10005-002), and National Natural Science Fundation of China (No. U0832601) to Y.T.Z.
收录类别	SCI
语种	英语
资助者	This work was partially supported by grants from the Canadian Institutes of Health Research (No. HOP-86863) and NSERC (No. RGPIN/355310-2008) to D.J.D. D.J.D. is the recipient of a CIHR New Investigator Award and Dalhousie Medical Research Foundation New Investigator Award. This work was also partially supported by grants from National Basical Research Program of China (No.2009CB522306), Eleven Five-Year Key Scientific and Technological Program of China (No. 2009ZX09501-029, 2008ZX10001-015, 2008ZX10005-002), and National Natural Science Fundation of China (No. U0832601) to Y.T.Z. ; This work was partially supported by grants from the Canadian Institutes of Health Research (No. HOP-86863) and NSERC (No. RGPIN/355310-2008) to D.J.D. D.J.D. is the recipient of a CIHR New Investigator Award and Dalhousie Medical Research Foundation New Investigator Award. This work was also partially supported by grants from National Basical Research Program of China (No.2009CB522306), Eleven Five-Year Key Scientific and Technological Program of China (No. 2009ZX09501-029, 2008ZX10001-015, 2008ZX10005-002), and National Natural Science Fundation of China (No. U0832601) to Y.T.Z. ; This work was partially supported by grants from the Canadian Institutes of Health Research (No. HOP-86863) and NSERC (No. RGPIN/355310-2008) to D.J.D. D.J.D. is the recipient of a CIHR New Investigator Award and Dalhousie Medical Research Foundation New Investigator Award. This work was also partially supported by grants from National Basical Research Program of China (No.2009CB522306), Eleven Five-Year Key Scientific and Technological Program of China (No. 2009ZX09501-029, 2008ZX10001-015, 2008ZX10005-002), and National Natural Science Fundation of China (No. U0832601) to Y.T.Z. ; This work was partially supported by grants from the Canadian Institutes of Health Research (No. HOP-86863) and NSERC (No. RGPIN/355310-2008) to D.J.D. D.J.D. is the recipient of a CIHR New Investigator Award and Dalhousie Medical Research Foundation New Investigator Award. This work was also partially supported by grants from National Basical Research Program of China (No.2009CB522306), Eleven Five-Year Key Scientific and Technological Program of China (No. 2009ZX09501-029, 2008ZX10001-015, 2008ZX10005-002), and National Natural Science Fundation of China (No. U0832601) to Y.T.Z.
WOS记录号	WOS:000299337800006
引用统计	被引频次：7[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/353002/6877
专题	科研部门_分子免疫药理学（郑永唐）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	denis.dupre@dal.ca
作者单位	1.Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada 2.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, P. R. China
推荐引用方式 GB/T 7714	Kuang YQ,Pang W,Zheng YT,et al. NHERF1 regulates gp120-induced internalization and signaling by CCR5, and HIV-1 production[J]. EUROPEAN JOURNAL OF IMMUNOLOGY,2012,42(2):299-310.
APA	Kuang YQ,Pang W,Zheng YT,Dupre DJ*,&denis.dupre@dal.ca.(2012).NHERF1 regulates gp120-induced internalization and signaling by CCR5, and HIV-1 production.EUROPEAN JOURNAL OF IMMUNOLOGY,42(2),299-310.
MLA	Kuang YQ,et al."NHERF1 regulates gp120-induced internalization and signaling by CCR5, and HIV-1 production".EUROPEAN JOURNAL OF IMMUNOLOGY 42.2(2012):299-310.

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