scholarly journals Paxillin Associates with the Microtubule Cytoskeleton and the Immunological Synapse of CTL through Its Leucine-Aspartic Acid Domains and Contributes to Microtubule Organizing Center Reorientation

2011 ◽  
Vol 187 (11) ◽  
pp. 5824-5833 ◽  
Author(s):  
Leslie K. Robertson ◽  
Hanne L. Ostergaard
Keyword(s):  
Aspartic Acid ◽  
Immunological Synapse ◽  
Microtubule Organizing Center ◽  
Microtubule Cytoskeleton ◽  
Organizing Center

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 Paxillin Localizes to the Lymphocyte Microtubule Organizing Center and Associates with the Microtubule Cytoskeleton

2000 ◽  
Vol 275 (34) ◽  
pp. 26436-26440 ◽  
Author(s):  
Lourdes Herreros ◽  
José Luis Rodrı́guez-Fernández ◽  
Michael C. Brown ◽  
José L. Alonso-Lebrero ◽  
Carlos Cabañas ◽  
...  
Keyword(s):  
Microtubule Organizing Center ◽  
Microtubule Cytoskeleton ◽  
Organizing Center

scholarly journals AMF-R Tubules Concentrate in a Pericentriolar Microtubule Domain After MSV Transformation of Epithelial MDCK Cells

1997 ◽  
Vol 45 (10) ◽  
pp. 1351-1363 ◽  
Author(s):  
Ivan R. Nabi ◽  
Ginette Guay ◽  
Danièle Simard
Keyword(s):  
Mdck Cells ◽  
Cell Periphery ◽  
Perinuclear Region ◽  
Microtubule Organizing Center ◽  
Autocrine Motility Factor ◽  
Microtubule Cytoskeleton ◽  
Motility Factor ◽  
Organizing Center ◽  
Sarcoma Virus ◽  
Moloney Sarcoma Virus

Autocrine motility factor receptor (AMF-R) is localized to an intracellular microtubule-associated membranous organelle, the AMF-R tubule. In well-spread untrans-formed MDCK epithelial cells, the microtubules originate from a broad perinuclear region and AMF-R tubules extend throughout the cytoplasm of the cells. In Moloney sarcoma virus (mos)-transformed MDCK (MSV-MDCK) cells, microtubules accumulate around the centrosome, forming a microtubule domain rich in stabilized detyrosinated microtubules. AMF-R tubules are quantitatively associated with this pericentriolar microtubule domain and the rough endoplasmic reticulum and lysosomes also co-distribute with the pericentriolar mass of microtubules. The Golgi apparatus is closely associated with the microtubule organizing center (MTOC) within the juxtanuclear mass of AMF-R tubules, and no co-localization of AMF-R tubules with the Golgi marker β-COP could be detected by confocal microscopy. After nocodazole treatment and washout, microtubule nucleation occurs exclusively at the centrosome of MSV-MDCK cells, and only after microtubule extension to the cell periphery does the microtubule cytoskeleton reorganize to generate the pericentriolar microtubule domain after 30–60 min. AMF-R tubules dispersed by nocodazole treatment concentrate in the pericentriolar region in parallel with the reorganization of the microtubule cytoskeleton. MSV transformation of epithelial MDCK cells results in the stabilization of a pericentriolar microtubule domain responsible for the concentration and polarized distribution of AMF-R tubules.

scholarly journals Stochastic model of T Cell repolarization during target elimination (II)

2021 ◽  
Author(s):  
Ivan Hornak ◽  
Heiko Rieger
Keyword(s):  
T Cell ◽  
Immunological Synapse ◽  
Molecular Motor ◽  
Initial Position ◽  
Cell Polarization ◽  
Target Cells ◽  
Microtubule Organizing Center ◽  
Tight Contact ◽  
Organizing Center ◽  
Arbitrary Position

Cytotoxic T lymphocytes (T cells) and natural killer cells form a tight contact, the immunological synapse (IS), with target cells, where they release their lytic granules containing perforin/granzyme and cytokine containing vesicles. During this process the cell repolarizes and moves the microtubule organizing center (MTOC) towards the IS. In the first part of our work we developed a computational model for the molecular-motor-driven motion of the MT cytoskeleton confined between plasma membrane and nucleus during T cell polarization and analyzed different mechanisms (cortical sliding and capture-shrinkage) that have been proposed on the basis of recent experiments. Here we use this model to analyze the dynamics of the MTOC during the repositioning process in situations in which a) the IS is in an arbitrary position with respect to the initial position of the MTOC and b) the T cell has two IS at two arbitrary positions. We observe several scenarios that have also been reported experimentally: the MTOC alternates stochastically (but with a well defined average transition time) between the two IS; it wiggles in between the two IS without transiting to one of the two; or it is at some point pulled to one of the two IS and stays there. Our model allows to predict which scenario emerges in dependency of the mechanisms in action and the number of dyneins present.

scholarly journals Cytokine Secretion by CD4+ T Cells at the Immunological Synapse Requires Cdc42-Dependent Local Actin Remodeling but Not Microtubule Organizing Center Polarity

2012 ◽  
Vol 189 (5) ◽  
pp. 2159-2168 ◽  
Author(s):  
Karine Chemin ◽  
Armelle Bohineust ◽  
Stéphanie Dogniaux ◽  
Marie Tourret ◽  
Sarah Guégan ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Immunological Synapse ◽  
Cytokine Secretion ◽  
Microtubule Organizing Center ◽  
Actin Remodeling ◽  
Organizing Center

scholarly journals A central role for microtubules in the differentiation of Drosophila oocytes

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1169-1180 ◽  
Author(s):  
W.E. Theurkauf ◽  
B.M. Alberts ◽  
Y.N. Jan ◽  
T.A. Jongens
Keyword(s):  
Microtubule Assembly ◽  
Nurse Cells ◽  
Microtubule Organizing Center ◽  
Microtubule Cytoskeleton ◽  
Recessive Mutations ◽  
Specific Accumulation ◽  
Organizing Center ◽  
Cytoplasmic Bridges ◽  
Oocyte Differentiation ◽  
Insight Into

Drosophila oocytes develop within cysts containing 16 cells that are interconnected by cytoplasmic bridges. Although the cysts are syncytial, the 16 cells differentiate to form a single oocyte and 15 nurse cells, and several mRNAs that are synthesized in the nurse cells accumulate specifically in the oocyte. To gain insight into the mechanisms that generate the cytoplasmic asymmetry within these cysts, we have examined cytoskeletal organization during oocyte differentiation. Shortly after formation of the 16 cell cysts, a prominent microtubule organizing center (MTOC) is established within the syncytial cytoplasm, and at the time the oocyte is determined, a single microtubule cytoskeleton connects the oocyte with the remaining 15 cells of each cyst. Recessive mutations at the Bicaudal-D (Bic-D) and egalitarian (egl) loci, which block oocyte differentiation, disrupt formation and maintenance of this polarized microtubule cytoskeleton. Microtubule assembly-inhibitors phenocopy these mutations, and prevent oocyte-specific accumulation of oskar, cyclin B and 65F mRNAs. We propose that formation of the polarized microtubule cytoskeleton is required for oocyte differentiation, and that this structure mediates the asymmetric accumulation of mRNAs within the syncytial cysts.

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.

Three-Dimensional reconstruction of isolated centrosomes by automated electron tomography

1994 ◽  
Vol 52 ◽  
pp. 310-311
Author(s):  
M.B. Braunfeld ◽  
M. Moritz ◽  
B.M. Alberts ◽  
J.W. Sedat ◽  
D.A. Agard
Keyword(s):  
Electron Tomography ◽  
Three Dimensional ◽  
Vital Role ◽  
Complex Nature ◽  
Animal Cells ◽  
Microtubule Organizing Center ◽  
Nucleation Sites ◽  
Dimensional Reconstruction ◽  
Organizing Center ◽  
Resolution Model

In animal cells, the centrosome functions as the primary microtubule organizing center (MTOC). As such the centrosome plays a vital role in determining a cell's shape, migration, and perhaps most importantly, its division. Despite the obvious importance of this organelle little is known about centrosomal regulation, duplication, or how it nucleates microtubules. Furthermore, no high resolution model for centrosomal structure exists.We have used automated electron tomography, and reconstruction techniques in an attempt to better understand the complex nature of the centrosome. Additionally we hope to identify nucleation sites for microtubule growth.Centrosomes were isolated from early Drosophila embryos. Briefly, after large organelles and debris from homogenized embryos were pelleted, the resulting supernatant was separated on a sucrose velocity gradient. Fractions were collected and assayed for centrosome-mediated microtubule -nucleating activity by incubating with fluorescently-labeled tubulin subunits. The resulting microtubule asters were then spun onto coverslips and viewed by fluorescence microscopy.

Sign in / Sign up

Export Citation Format

Share Document