Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase CDC42.
The mechanisms by which cells rapidly polarize in the direction of external signals are not understood. Helper T cells, when contacted by an antigen-presenting cell, polarize their cytoskeletons toward the antigen-presenting cell within minutes. Here we show that, in T cells, the mammalian Ras-related GTPase CDC42 (the homologue of yeast CDC42, a protein involved in budding polarity) can regulate the polarization of both actin and microtubules toward antigen-presenting cells but is not involved in other T-cell signaling processes such as those which culminate in interleukin 2 production. Although T-cell polarization appears dispensable for signaling leading to interleukin 2 production, polarization may direct lymphokine secretion towards the correct antigen-presenting cell in a crowded cellular environment. Inhibitor experiments suggest that phosphatidylinositol 3-kinase is required for cytoskeletal polarization but that calcineurin activity, known to be important for other aspects of signaling, is not. Apparent conservation of CDC42 function between yeast and T cells suggests that this GTPase is a general regulator of cytoskeletal polarity in many cell types.
Stowers
L
L
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Yelon
D
D
Berg
L J
LJ
Chant
J
J
D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000483:Alleles; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology* / Q000648:ultrastructure; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D017931:DNA Primers; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D016393:Lymphoma, B-Cell; D051379:Mice; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D008961:Models, Structural; D008969:Molecular Sequence Data; D017354:Point Mutation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D014162:Transfection; D014407:Tumor Cells, Cultured; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
D000199:Actins; D018797:Cell Cycle Proteins; D017931:DNA Primers; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae