Specific recruitment of SPA-1 to the immunological synapse: involvement of actin-bundling protein actinin.
SPA-1 is involved in the regulation of T cell activation in response to antigens through the control of Rap1 GTPase signaling. In this study, the subcellular localization of SPA-1 in the T cells was examined by using anti-SPA-1 antibody and GFP-SPA-1. While SPA-1 was detected diffusely at the surface cortical region in the floating unpolarized T cells, it was concentrated at the matrix-adhesion region with dense actin-cytoskeleton. Upon interaction with specific antigen-presenting cells, SPA-1 was highly concentrated at the immunological synapse closely co-localizing with actin. By yeast two-hybrid system, SPA-1 was shown to interact with an actin-bundling protein alpha-actinin, and it was indicated that SPA-1 co-localized with alpha-actinin at the immunological synapse. The results have suggested that SPA-1 in the T cells is selectively recruited to the immunological synapse with dense actin-cytoskeletal reorganization and keeps restraining the levels of Rap1GTP at the local TCR-signaling complex for the T cell activation.
Harazaki
Masashi
M
Department of Pediatrics, Graduate School of Medicine, Kyoto, Japan.
Kawai
Yohei
Y
Su
Li
L
Hamazaki
Yoko
Y
Nakahata
Tatsutoshi
T
Minato
Nagahiro
N
Hattori
Masakazu
M
D000185:Actinin / Q000276:immunology / Q000378:metabolism*; D000199:Actins / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins / Q000276:immunology*; D007110:Immunity, Active / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009687:Nuclear Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D020798:Two-Hybrid System Techniques; D020827:rap1 GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism
D000199:Actins; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C091108:Sipa1 protein, mouse; D000185:Actinin; D020827:rap1 GTP-Binding Proteins