scholarly journals The Polarity Protein Par1b/EMK/MARK2 Regulates T Cell Receptor-Induced Microtubule-Organizing Center Polarization

2009 ◽  
Vol 183 (2) ◽  
pp. 1215-1221 ◽  
Author(s):  
Joseph Lin ◽  
Kirk K. Hou ◽  
Helen Piwnica-Worms ◽  
Andrey S. Shaw
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Microtubule Organizing Center ◽  
Organizing Center

scholarly journals Actin reorganization at the centrosomal area and the immune synapse regulates polarized secretory traffic of multivesicular bodies in T lymphocytes

2020 ◽  
Author(s):  
Ana Bello-Gamboa ◽  
Marta Velasco ◽  
Solange Moreno ◽  
Gonzalo Herranz ◽  
Roxana Ilie ◽  
...  
Keyword(s):  
T Cell ◽  
Actin Cytoskeleton ◽  
Cell Receptor ◽  
Multivesicular Bodies ◽  
Microtubule Organizing Center ◽  
Independent Manner ◽  
Actin Reorganization ◽  
Immune Synapse ◽  
Cell Clones ◽  
Organizing Center

ABSTRACTT-cell receptor stimulation induces the convergence of multivesicular bodies towards the microtubule-organizing center (MTOC) and the polarization of the MTOC to the immune synapse (IS). These events lead to exosome secretion at the IS. We describe here that upon IS formation centrosomal area F-actin decreased concomitantly with MTOC polarization to the IS. PKCδ-interfered T cell clones showed a sustained level of centrosomal area F-actin associated with defective MTOC polarization. We analysed the contribution of two actin cytoskeleton-regulatory proteins, FMNL1 and paxillin, to the regulation of cortical and centrosomal F-actin networks. FMNL1β phosphorylation and F-actin reorganization at the IS were inhibited in PKCδ-interfered clones. F-actin depletion at the central region of the IS, a requirement for MTOC polarization, was associated with FMNL1β phosphorylation at its C-terminal, autoregulatory region. Interfering all FMNL1 isoforms prevented MTOC polarization; nonetheless, FMNL1β re-expression restored MTOC polarization in a centrosomal area F-actin reorganization-independent manner. Moreover, PKCδ-interfered clones exhibited decreased paxillin phosphorylation at the MTOC, which suggests an alternative actin cytoskeleton regulatory pathway. Our results infer that PKCδ regulates MTOC polarization and secretory traffic leading to exosome secretion in a coordinated manner by means of two distinct pathways, one involving FMNL1β regulation and controlling F-actin reorganization at the IS, and the other, comprising paxillin phosphorylation potentially controlling centrosomal area F-actin reorganization.

scholarly journals An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes

2008 ◽  
Vol 205 (13) ◽  
pp. 3201-3213 ◽  
Author(s):  
Olga Antón ◽  
Alicia Batista ◽  
Jaime Millán ◽  
Laura Andrés-Delgado ◽  
Rosa Puertollano ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
T Cell ◽  
Immunological Synapse ◽  
Cell Receptor ◽  
T Cell Signaling ◽  
Microtubule Organizing Center ◽  
Transport Pathway ◽  
Specific Transport ◽  
Transport Vesicles ◽  
Organizing Center

The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 transcription. To investigate the mechanism by which MAL regulates Lck targeting, we analyzed the dynamics of Lck and found that it travels to the plasma membrane in specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated an association of MAL with Lck. Both carrier formation and partitioning of Lck into detergent-insoluble membranes were ablated in the absence of MAL. Polarization of T cell receptor for antigen (TCR) and microtubule-organizing center to immunological synapse (IS) were also defective. Although partial correction of the latter defects was possible by forced expression of Lck at the plasma membrane, their complete correction, formation of transport vesicles, partitioning of Lck, and restoration of signaling pathways, which are required for IL-2 transcription up-regulation, were achieved by exogenous expression of MAL. We concluded that MAL is required for recruitment of Lck to specialized membranes and formation of specific transport carriers for Lck targeting. This novel transport pathway is crucial for TCR-mediated signaling and IS assembly.

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