Journal ArticleDOI
Centrosome polarization delivers secretory granules to the immunological synapse
TLDR
These data show that CTLs use a previously unreported mechanism for delivering secretory granules to the immunological synapse, with granule secretion controlled by centrosome delivery to the plasma membrane.Abstract:
Cytotoxic T lymphocytes (CTLs) destroy virally infected and tumorigenic cells by releasing the contents of specialized secretory lysosomes--termed 'lytic granules'--at the immunological synapse formed between the CTL and the target. On contact with the target cell, the microtubule organizing centre of the CTL polarizes towards the target and granules move along microtubules in a minus-end direction towards the polarized microtubule organizing centre. However, the final steps of secretion have remained unclear. Here we show that CTLs do not require actin or plus-end microtubule motors for secretion, but instead the centrosome moves to and contacts the plasma membrane at the central supramolecular activation cluster of the immunological synapse. Actin and IQGAP1 are cleared away from the synapse, and granules are delivered directly to the plasma membrane. These data show that CTLs use a previously unreported mechanism for delivering secretory granules to the immunological synapse, with granule secretion controlled by centrosome delivery to the plasma membrane.read more
Citations
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Journal ArticleDOI
Lysosomes: fusion and function
TL;DR: Lysosomes are dynamic organelles that receive and degrade macromolecules from the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways, as well as having more specialized secretory functions in some cell types.
Journal ArticleDOI
Controlling Natural Killer Cell Responses: Integration of Signals for Activation and Inhibition
TL;DR: Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing.
Journal ArticleDOI
Centrioles, centrosomes, and cilia in health and disease.
Erich A. Nigg,Jordan W. Raff +1 more
TL;DR: Recent advances in understanding of the function and biogenesis of centriole organelles are reviewed, and their connection to human disease is emphasized.
Journal ArticleDOI
Perforin and granzymes: function, dysfunction and human pathology
Ilia Voskoboinik,Ilia Voskoboinik,James C. Whisstock,James C. Whisstock,Joseph A. Trapani,Joseph A. Trapani +5 more
TL;DR: The current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology is discussed, beginning to define and understand a range of human diseases that are associated with a failure to deliver active per forin to target cells.
Journal ArticleDOI
Natural Killer Cells: Development, Maturation, and Clinical Utilization
Alex M. Abel,Alex M. Abel,Chao Yang,Chao Yang,Monica S. Thakar,Monica S. Thakar,Subramaniam Malarkannan +6 more
TL;DR: Recent advances made in the understanding of how NK cells develop, mature, and their potential translational use in the clinic are summarized.
References
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Journal ArticleDOI
Three-dimensional segregation of supramolecular activation clusters in T cells
TL;DR: The three-dimensional distribution of receptors and intracellular proteins that cluster at the contacts between T cells and APCs during antigen-specific interactions, Surprisingly, instead of showing uniform oligomerization, these proteins clustered into segregated three- dimensional domains within the cell contacts.
Journal ArticleDOI
The Immunological Synapse of CTL Contains a Secretory Domain and Membrane Bridges
TL;DR: It is shown that although target cell death occurs within 5 min of CTL-target cell contact, an immunological synapse similar to that seen in CD4 cells rapidly forms in CTL, with a ring of adhesion proteins surrounding an inner signaling molecule domain.
Journal ArticleDOI
Reconstructions of Centriole Formation and Ciliogenesis in Mammalian Lungs
TL;DR: Reconstruction of the processes of centriolar formation and ciliogenesis based on evidence found in electron micrographs of tissues and organ cultures obtained chiefly from the lungs of foetal rats leads to an interpretation of the centriole as a semi-autonomous organelle whose replicative capacity is separable from the characteristic triplet fibre structure of its wall.
Journal ArticleDOI
The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors
Ingrid Jordens,Mar Fernandez-Borja,Marije Marsman,Simone Dusseljee,Lennert Janssen,Jero Calafat,Hans Janssen,Richard Wubbolts,Jacques Neefjes +8 more
TL;DR: It is shown that RILP prevents further cycling of Rab7 and induces the recruitment of functional dynein-dynactin motor complexes to Rab7-containing late endosomes and lysosomes.
Journal ArticleDOI
Rac1 and Cdc42 Capture Microtubules through IQGAP1 and CLIP-170
Masaki Fukata,Takashi Watanabe,Jun Noritake,Masato Nakagawa,Masaki Yamaga,Shinya Kuroda,Yoshiharu Matsuura,Akihiro Iwamatsu,Franck Perez,Kozo Kaibuchi +9 more
TL;DR: Results indicate that Rac1/Cdc42 marks special cortical spots where the IQGAP1 and CLIP-170 complex is targeted, leading to a polarized microtubule array and cell polarization.