Specific patterns of Cdc42 activity are related to distinct elements of T cell polarization.
T cell polarization toward and within the cellular interface with an APC is critical for effective T cell activation. The Rho family GTPase Cdc42 is a central regulator of cellular polarization. Using live-cell imaging, we characterized the spatiotemporal patterns of Cdc42 activity and their physiological regulation. Using three independent means of experimental manipulation of Cdc42 activity, we established that Cdc42 is a critical regulator of T cell actin dynamics, TCR clustering, and cell cycle entry. Using quantification of three-dimensional data, we could relate distinct spatiotemporal patterns of Cdc42 activity to specific elements of T cell activation. This result suggests that Cdc42 activity in specific locations at specific times is most critical for its function in T cell activation.
Tskvitaria-Fuller
Irina
I
Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Seth
Abhinav
A
Mistry
Neeta
N
Gu
Hua
H
Rosen
Michael K
MK
Wülfing
Christoph
C
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D050721:Proto-Oncogene Proteins c-cbl / Q000502:physiology; D011940:Receptor Aggregation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; C118387:Cblb protein, mouse; D011948:Receptors, Antigen, T-Cell; D050721:Proto-Oncogene Proteins c-cbl; D020764:cdc42 GTP-Binding Protein