Role of Rho-family GTPase Cdc42 in polarized expression of lymphocyte appendages

Journal of Leukocyte Biology

Stuart Ratner¹  Marie P. Piechocki²  Anne Galy³ 

[1] Breast Cancer Research Program and Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan Breast Cancer Research Program and Breast Cancer Research Program and Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan Breast Cancer Research Program and Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan;Breast Cancer Research Program and Breast Cancer Research Program and Breast Cancer Research Program and;Stem Cell Transplantation Program, Barbara Ann Karmanos Cancer Institute, and Stem Cell Transplantation Program, Barbara Ann Karmanos Cancer Institute, and Stem Cell Transplantation Program, Barbara Ann Karmanos Cancer Institute, and

关键词: human;    T cell;    leukemia;    motility;    chemotaxis;    cytoskeleton;   

DOI  :  10.1189/jlb.1001894

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Lymphocytes polarize for motility by developing a broad anterior, where lamellipodia arise, and a simple stalk-like posterior appendage, the uropod. Through time-lapse analysis of normal and leukemic human T cells, it was found that this polarized form is maintained by a mechanism that excludes lamellipodia from the uropod. Lamellipodia regularly traveled rearward to encroach upon the uropod but disassembled abruptly at the uropod border. This exclusion of lamellipodia from the uropod required the Rho-family guanosine triphosphatase Cdc42. Reduction of Cdc42 activity by expression of dominant-negative Cdc42 resulted in “two headed” cells in which lamellipodia persisted at the distal end of the uropod. Random and chemotactic motility were impaired. Increased Cdc42 activity, induced by expression of activated, mutant Cdc42, was accompanied by a general loss of lamellipodia. The results suggest that one role of Cdc42 in lymphocyte motility is to preserve polarity by concentrating lamellipodial disassembly signals in the uropod.

【 授权许可】

Unknown