The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization.
Cell polarization is required for virtually all functions of T cells, including transendothelial migration in response to chemokines. However, the molecular pathways that establish T cell polarity are poorly understood. We show that the activation of the partitioning defective (Par) polarity complex is a key event during Rap1- and chemokine-induced T cell polarization. Intracellular localization and activation of the Par complex are initiated by Rap1 and require Cdc42 activity. The Rac activator Tiam1 associates with both Rap1 and components of the Par complex, and thereby may function to connect the Par polarity complex to Rap1 and to regulate the Rac-mediated actin remodelling required for T cell polarization. Consistent with these findings, Tiam1-deficient T cells are impaired in Rap1- and chemokine-induced polarization and chemotaxis. Our studies implicate Tiam1 and the Par polarity complex in polarization of T cells, and provide a mechanism by which chemokines and Rap1 regulate T cell polarization and chemotaxis.
Gérard
Audrey
A
Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
Mertens
Alexander E E
AE
van der Kammen
Rob A
RA
Collard
John G
JG
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000502:physiology*; D018925:Chemokines / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D020764:cdc42 GTP-Binding Protein / Q000032:analysis / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D018925:Chemokines; D020662:Guanine Nucleotide Exchange Factors; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D011493:Protein Kinase C; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D020764:cdc42 GTP-Binding Protein; D020827:rap1 GTP-Binding Proteins; D000099221:Protein Kinase C zeta; C497483:CD44 protein, human; C509689:PARD3 protein, human; C087334:TIAM1 protein, human