title: Actin nucleation at the centrosome controls lymphocyte polarity.
abstract: Cell polarity is required for the functional specialization of many cell types including lymphocytes. A hallmark of cell polarity is the reorientation of the centrosome that allows repositioning of organelles and vesicles in an asymmetric fashion. The mechanisms underlying centrosome polarization are not fully understood. Here we found that in resting lymphocytes, centrosome-associated Arp2/3 locally nucleates F-actin, which is needed for centrosome tethering to the nucleus via the LINC complex. Upon lymphocyte activation, Arp2/3 is partially depleted from the centrosome as a result of its recruitment to the immune synapse. This leads to a reduction in F-actin nucleation at the centrosome and thereby allows its detachment from the nucleus and polarization to the synapse. Therefore, F-actin nucleation at the centrosome--regulated by the availability of the Arp2/3 complex--determines its capacity to polarize in response to external stimuli.
authors.affiliation: INSERM-U932 Immunité et Cancer, Institut Curie, PSL Research University, 75248 Paris Cedex 05, France.
authors.forename: Dorian
authors.initials: D
authors.lastname: Obino
authors.affiliation: CytoMorpho Lab, Biosciences &Biotechnology Institute of Grenoble, UMR5168, CEA/INRA/CNRS/Université Grenoble-Alpes, Grenoble 38054, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Farina
authors.affiliation: INSERM-U932 Immunité et Cancer, Institut Curie, PSL Research University, 75248 Paris Cedex 05, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Malbec
authors.affiliation: INSERM-U932 Immunité et Cancer, Institut Curie, PSL Research University, 75248 Paris Cedex 05, France.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Sáez
authors.affiliation: INSERM-U932 Immunité et Cancer, Institut Curie, PSL Research University, 75248 Paris Cedex 05, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Maurin
authors.affiliation: CytoMorpho Lab, Biosciences &Biotechnology Institute of Grenoble, UMR5168, CEA/INRA/CNRS/Université Grenoble-Alpes, Grenoble 38054, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Gaillard
authors.affiliation: Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie, PSL Research University, 75248 Paris Cedex 05, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dingli
authors.affiliation: Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie, PSL Research University, 75248 Paris Cedex 05, France.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: Ecole Polytechnique, CNRS UMR7654, Palaiseau 91120, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Gautreau
authors.affiliation: Departamento de Biologia Celular y Molecular, Pontificia Universidad Catolica de Chile, Santiago 6513677, Chile.
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Yuseff
authors.affiliation: CytoMorpho Lab, Biosciences &Biotechnology Institute of Grenoble, UMR5168, CEA/INRA/CNRS/Université Grenoble-Alpes, Grenoble 38054, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Blanchoin
authors.affiliation: CytoMorpho Lab, Biosciences &Biotechnology Institute of Grenoble, UMR5168, CEA/INRA/CNRS/Université Grenoble-Alpes, Grenoble 38054, France.|CytoMorpho Lab, Hopital Saint Louis, Institut Universitaire d'Hematologie, UMRS1160, CEA/INSERM/Université Paris Diderot, Paris 75010, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Théry
authors.affiliation: INSERM-U932 Immunité et Cancer, Institut Curie, PSL Research University, 75248 Paris Cedex 05, France.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Lennon-Duménil
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism*; D015536:Down-Regulation; D054992:Immunological Synapses / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D020543:Proteome / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D020543:Proteome; D011947:Receptors, Antigen, B-Cell