scholarly journals Cdc42-interacting protein–4 functionally links actin and microtubule networks at the cytolytic NK cell immunological synapse

2007 ◽  
Vol 178 (6) ◽  
pp. i13-i13 ◽  
Author(s):  
Pinaki P. Banerjee ◽  
Rahul Pandey ◽  
Rena Zheng ◽  
Megan M. Suhoski ◽  
Linda Monaco-Shawver ◽  
...  
Keyword(s):  
Immunological Synapse ◽  
Nk Cell ◽  
Interacting Protein ◽  
Microtubule Networks

scholarly journals Cdc42-interacting protein–4 functionally links actin and microtubule networks at the cytolytic NK cell immunological synapse

2007 ◽  
Vol 204 (10) ◽  
pp. 2305-2320 ◽  
Author(s):  
Pinaki P. Banerjee ◽  
Rahul Pandey ◽  
Rena Zheng ◽  
Megan M. Suhoski ◽  
Linda Monaco-Shawver ◽  
...  
Keyword(s):  
Actin Filament ◽  
Cell Activation ◽  
Immunological Synapse ◽  
Nk Cell ◽  
Filamentous Actin ◽  
Microtubule Organizing Center ◽  
Interacting Protein ◽  
Lytic Granules ◽  
Organizing Center ◽  
Microtubule Networks

An essential function of the immunological synapse (IS) is directed secretion. NK cells are especially adept at this activity, as they direct lytic granules to the synapse for secretion, which enables cytotoxicity and facilitates host defense. This initially requires rearrangement of the actin cytoskeleton and, subsequently, microtubule-dependent trafficking of the lytic granules. As these two steps are sequential, specific linkages between them are likely to serve as critical regulators of cytotoxicity. We studied Cdc42-interacting protein–4 (CIP4), which constitutively interacts with tubulin and microtubules but focuses to the microtubule organizing center (MTOC) after NK cell activation, when it is able to associate with Wiskott-Aldrich syndrome protein (WASp) and the actin filament–rich IS. WASp deficiency, overexpression of CIP4, or parts of CIP4 interfere with this union and block normal CIP4 localization, MTOC polarization to the IS, and cytotoxicity. Reduction of endogenous CIP4 expression using small interfering RNA similarly inhibits MTOC polarization and cytotoxic activity but does not impair actin filament accumulation at the IS, or Cdc42 activation. Thus, CIP4 is an important cytoskeletal adaptor that functions after filamentous actin accumulation and Cdc42 activation to enable MTOC polarization and NK cell cytotoxicity.

scholarly journals LFA-1 and CD2 Synergize for the Erk1/2 Activation in the Natural Killer (NK) Cell Immunological Synapse

2009 ◽  
Vol 284 (32) ◽  
pp. 21280-21287 ◽  
Author(s):  
Xiaodong Zheng ◽  
Yanyan Wang ◽  
Haiming Wei ◽  
Rui Sun ◽  
Zhigang Tian
Keyword(s):  
Natural Killer ◽  
Immunological Synapse ◽  
Nk Cell

scholarly journals AKAP350 regulates cytoskeleton remodeling and LFA-1 organization during NK cytolytic response

2020 ◽  
Author(s):  
Alejandro P. Pariani ◽  
Evangelina Almada ◽  
Florencia Hidalgo ◽  
Carla Borini-Etichetti ◽  
Rodrigo Vena ◽  
...  
Keyword(s):  
Golgi Apparatus ◽  
Nk Cell ◽  
Cell Interaction ◽  
Cytolytic Activity ◽  
Microtubule Dynamics ◽  
Interacting Protein ◽  
Immune Synapse ◽  
Cytoskeleton Remodeling ◽  
First Time ◽  
Cytolytic Response

AbstractNatural killer (NK) cell cytotoxicity requires extensive cytoskeleton remodeling and receptors reorganization at the site of NK/target cell interaction (immune synapse, IS). How these processes are integrated remains unclear. We found that AKAP350, a scaffold protein that regulates microtubule dynamics, was required for NK cytolytic activity. Reduction of AKAP350 expression inhibited actin and LFA-1 reorganization and centrosome translocation to the IS. AKAP350KD cells showed decreased microtubule nucleation at the Golgi apparatus and reduced localization at the centrosome and at the IS of CIP4, an AKAP350 interacting protein that regulates centrosome translocation to the IS. AKAP350 delocalization from the Golgi or pharmacological disruption of microtubule dynamics or Golgi function impaired LFA-1 clustering at the IS, preserving actin remodeling. These data support a role for AKAP350 in the integration of actin and microtubule remodeling during NK activation and reveal for the first time the participation of the Golgi apparatus in NK-IS maturation.

scholarly journals Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the murine immunological synapse

2018 ◽  
Vol 3 ◽  
pp. 84 ◽  
Author(s):  
Chiara Beilin ◽  
Kaushik Choudhuri ◽  
Gerben Bouma ◽  
Dessislava Malinova ◽  
Jaime Llodra ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immunological Synapse ◽  
Nk Cell ◽  
Severe Combined Immunodeficiency ◽  
Cd4 T Cell ◽  
Gamma Chain

Background:Mutations of the common cytokine receptor gamma chain (γc) cause Severe Combined Immunodeficiency characterized by absent T and NK cell development. Although stem cell therapy restores these lineages, residual immune defects are observed that may result from selective persistence of γc-deficiency in myeloid lineages. However, little is known about the contribution of myeloid-expressed γc to protective immune responses.  Here we examine the importance of γc for myeloid dendritic cell (DC) function.Methods:We utilize a combination ofin vitroDC/T-cell co-culture assays and a novel lipid bilayer system mimicking the T cell surface to delineate the role of DC-expressed γc during DC/T-cell interaction.Results:We observed that γc in DC was recruited to the contact interface following MHCII ligation, and promoted IL-15Rα colocalization with engaged MHCII. Unexpectedly, trans-presentation of IL-15 was required for optimal CD4+T cell activation by DC and depended on DC γc expression. Neither recruitment of IL-15Rα nor IL-15 trans-signaling at the DC immune synapse (IS), required γc signaling in DC, suggesting that γc facilitates IL-15 transpresentation through induced intermolecularcisassociations or cytoskeletal reorganization following MHCII ligation.Conclusions:These findings show that DC-expressed γc is required for effective antigen-induced CD4+ T cell activation. We reveal a novel mechanism for recruitment of DC IL-15/IL-15Rα complexes to the IS, leading to CD4+ T cell costimulation through localized IL-15 transpresentation that is coordinated with antigen-recognition.

scholarly journals NK Cell Lytic Granules Are Highly Motile at the Immunological Synapse and Require F-Actin for Post-Degranulation Persistence

2012 ◽  
Vol 189 (10) ◽  
pp. 4870-4880 ◽  
Author(s):  
Emily M. Mace ◽  
Winona W. Wu ◽  
Tina Ho ◽  
Shaina S. Mann ◽  
Hsiang-Ting Hsu ◽  
...  
Keyword(s):  
Immunological Synapse ◽  
Nk Cell ◽  
Lytic Granules

Analysis of the NK Cell Immunological Synapse

2009 ◽  
pp. 127-148 ◽  
Author(s):  
Keri B. Sanborn ◽  
Gregory D. Rak ◽  
Ashley N. Mentlik ◽  
Pinaki P. Banerjee ◽  
Jordan S. Orange
Keyword(s):  
Immunological Synapse ◽  
Nk Cell

scholarly journals The Mitogen-Activated Protein Kinase Scaffold KSR1 Is Required for Recruitment of Extracellular Signal-Regulated Kinase to the Immunological Synapse

2009 ◽  
Vol 29 (6) ◽  
pp. 1554-1564 ◽  
Author(s):  
Emanuele Giurisato ◽  
Joseph Lin ◽  
Angus Harding ◽  
Elisa Cerutti ◽  
Marina Cella ◽  
...  
Keyword(s):  
Map Kinase ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Immunological Synapse ◽  
Nk Cell ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT KSR1 is a mitogen-activated protein (MAP) kinase scaffold that enhances the activation of the MAP kinase extracellular signal-regulated kinase (ERK). The function of KSR1 in NK cell function is not known. Here we show that KSR1 is required for efficient NK-mediated cytolysis and polarization of cytolytic granules. Single-cell analysis showed that ERK is activated in an all-or-none fashion in both wild-type and KSR1-deficient cells. In the absence of KSR1, however, the efficiency of ERK activation is attenuated. Imaging studies showed that KSR1 is recruited to the immunological synapse during T-cell activation and that membrane recruitment of KSR1 is required for recruitment of active ERK to the synapse.

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