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* Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104 and
Institut National de la Santé et de la Recherche Médicale, Unité 567, Paris, France
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), PKC
and PKC
, 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, and Ligue Nationale Contre le Cancer. E.R. is a recipient of a fellowship from the Portuguese Foundation for Science and Technology and a student from the Gulbenkian Ph.D. Program in Biomedicine.
2 Address correspondence and reprint requests to Dr. Jérôme Delon, Institut Cochin, Département de Biologie Cellulaire, Institut National de la Santé et de la Recherche Médicale, Unité 567, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, 22 Rue Méchain, 75014 Paris, France. E-mail address: delon{at}cochin.inserm.fr
3 Abbreviations used in this paper: HEV, high endothelial venule; aPKC, atypical protein kinase C; DC, dendritic cell; KD, kinase dead; NT, N terminal; PBT, peripheral blood T lymphocyte; PKC, protein kinase C; WT, wild type.
4 The online version of this article contains supplemental material.
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