Blood Journal
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Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex

  1. Mathieu Kurowska13,
  2. Nicolas Goudin2,3,
  3. Nadine T. Nehme13,
  4. Magali Court46,
  5. Jérôme Garin46,
  6. Alain Fischer13,7,
  7. Geneviève de Saint Basile13,7,*, and
  8. Gaël Ménasché13,*
  1. 1Inserm, Unité U768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Paris, France;
  2. 2Inserm, Institut Fédératif de Recherche Necker Enfants-Malades (IFR94), Université Paris Descartes, Paris, France;
  3. 3Imagine Institute, Paris, France;
  4. 4Inserm, Unité U1038, Grenoble, France;
  5. 5Commisariat à l'énergie atomique, Direction des sciences du vivant, Institut de Recherches en technologies et science du vivant, Laboratoire de Biologie à Grandes Echelle, Grenoble, France;
  6. 6Université Joseph Fourier, Grenoble, France; and
  7. 7Assistance Publique–Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Unité d'Immunologie-Hématologie Pédiatrique, Paris, France
This article has an Erratum 123(9):1432

Abstract

Cytotoxic T lymphocytes kill target cells via the polarized secretion of cytotoxic granules at the immune synapse. The lytic granules are initially recruited around the polarized microtubule-organizing center. In a dynein-dependent transport process, the granules move along microtubules toward the microtubule-organizing center in the minus-end direction. Here, we found that a kinesin-1–dependent process is required for terminal transport and secretion of polarized lytic granule to the immune synapse. We show that synaptotagmin-like protein 3 (Slp3) is an effector of Rab27a in cytotoxic T lymphocytes and interacts with kinesin-1 through the tetratricopeptide repeat of the kinesin-1 light chain. Inhibition of the Rab27a/Slp3/kinesin-1 transport complex impairs lytic granule secretion. Our data provide further molecular insights into the key functional and regulatory mechanisms underlying the terminal transport of cytotoxic granules and the latter's secretion at the immune synapse.

  • Submitted September 26, 2011.
  • Accepted January 30, 2012.
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