Cutting edge: Atypical PKCs regulate T lymphocyte polarity and scanning behavior.
Leukocyte locomotion is a polarized process with diverse regulatory assemblies segregating along an anterior-posterior axis that defines two regions within the cell, the leading edge and the uropod. However, the mechanisms that generate T cell asymmetry downstream of chemokine receptors are ill defined. In this study we show that the atypical protein kinases C (aPKCs), PKCiota and PKCzeta, are required for an early symmetry breaking step. Once the polarity is established, aPKCs also drive uropod formation. These effects depend on the interaction between Par6 and aPKCs. Finally, failure to transduce aPKC-dependent signals reduces T cell motility and their ability to scan dendritic cells. Altogether, our findings suggest that lymphocyte motor activity is regulated by a signaling cascade that relays chemokinetic input to aPKCs.
Real
Eliana
E
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France.
Faure
Sophie
S
Donnadieu
Emmanuel
E
Delon
Jérôme
J
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D004789:Enzyme Activation; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D000099221:Protein Kinase C zeta
D048868:Adaptor Proteins, Signal Transducing; D011493:Protein Kinase C; D054400:Receptors, CCR7; D000099221:Protein Kinase C zeta; C515370:CCR7 protein, human; C499657:PARD6A protein, human; C115015:PKC-3 protein