The newly found functions of MTOC in immunological response

Kloc, Małgorzata; Kubiak, Jacek Z.; Li, Xian Chang; Ghobrial, Rafik M.

doi:10.1189/jlb.0813468

Cited by 25 publications

(31 citation statements)

References 151 publications

(188 reference statements)

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“…Recent studies have shown that centrosome reorientation occurs during formation of the IS. IS formation is a necessary step within the immune response that includes membrane rearrangement at the sites where a T cell contacts an antigen-presenting cell (APC), resulting in activation of the T cell (Kloc et al 2013). Cytotoxic T lymphocyte (CTL) or natural killer (NK) cells form one type of IS that can eliminate infected or tumorigenic cells by releasing cytolytic granules.…”

Section: Centrosomes In the Immune Responsementioning

confidence: 99%

The Centrosome, a Multitalented Renaissance Organelle

Vertii

Hehnly

Doxsey

2016

Cold Spring Harb Perspect Biol

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The centrosome acts as a microtubule-organizing center (MTOC) from the G to G phases of the cell cycle; it can mature into a spindle pole during mitosis and/or transition into a cilium by elongating microtubules (MTs) from the basal body on cell differentiation or cell cycle arrest. New studies hint that the centrosome functions in more than MT organization. For instance, it has recently been shown that a specific substructure of the centrosome-the mother centriole appendages-are required for the recycling of endosomes back to the plasma membrane. This alone could have important implications for a renaissance in our understanding of the development of primary cilia, endosome recycling, and the immune response. Here, we review newly identified roles for the centrosome in directing membrane traffic, the immunological synapse, and the stress response.

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Section: Centrosomes In the Immune Responsementioning

confidence: 99%

The Centrosome, a Multitalented Renaissance Organelle

Vertii

Hehnly

Doxsey

2016

Cold Spring Harb Perspect Biol

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“…RNA was purified from primary cells using the RNeasy Plus Mini Kit (Qiagen) according to the manufacturer's instructions followed by cDNA synthesis using the Transcriptor First Strand cDNA Synthesis Kit (Roche) and the anchored-oligo(dT) 18 primer. Subsequently, quantitative real-time PCR (qRT-PCR) was performed using the LightCycler 480 SYBR Green I Master Kit (Roche) according to the manufacturer's protocol and the LightCycler 480 device.…”

Section: Quantitative Real-time Pcr (Qrt-pcr)mentioning

confidence: 99%

TCR signalling network organization at the immunological synapses of murine regulatory T cells

et al. 2017

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Regulatory T (Treg) cells require T-cell receptor (TCR) signalling to exert their immunosuppressive activity, but the precise organization of the TCR signalling network compared to conventional T (Tconv) cells remains elusive. By using accurate mass spectrometry and multi-epitope ligand cartography (MELC) we characterized TCR signalling and recruitment of TCR signalling components to the immunological synapse (IS) in www.eji-journal.euThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. 2Marco van Ham et al. Eur. J. Immunol. 2017. 0: 1-16 in Treg cells, thereby, seems to be differentially organized as in Tconv cells: Treg cells show reduced Ca 2+ flux and ERK1/2 phosphorylation upon TCR stimulation [6][7][8], and downstream signalling molecules such as Lck, LAT and PLCγ1 are essential for Treg cell suppressive capacity [9,10]. In this line, a novel TCRmediated ADAP/integrin-independent PLCγ1 activation pathway was described to be required for suppression of Tconv cells by Treg cells [11]. Furthermore, Treg cells exhibit reduced S473 phosphorylation of Akt which seems a prerequisite for suppression [12]. Although the enzymatic activity of the tyrosine kinase ZAP70 seems to be dispensable for the suppressive phenotype of Foxp3 + Treg cells [13], a single mutation within the SH2-domain of ZAP70 leads to impaired suppressive activities, which indicated its importance at the immunological synapse (IS) [14]. Finally, it has only recently been recognized that the recruitment of TCR signalling components into the IS is differentially organized in Treg cells and Tconv cells. The protein kinase PKCθ is recruited to the IS in Tconv cells, in Treg cells, however, this kinase was found to be sequestered away from the IS, but still of importance to control suppression [15]. The spatial recruitment of signalling components during IS formation critically depends on cytoskeleton dynamics, which in turn is controlled by TCR activation and subsequent phosphorylation of proteins regulating cytoskeleton reorganization [5]. As part of these processes the microtubule-organizing centre (MTOC) is rapidly translocated in proximity to the IS. MTOC repositioning depends on LAT, ZAP70 and SLP76 [16] and is regulated by a cascade of distinct isoforms of the family of novel protein kinase C (nPKC) [17]. The MTOC serves as a platform to coordinate molecular movements from and to the IS through the support of microtubule (MT) motors [18]. For instance, TCR microclusters move along MTs towards the centre of the IS in a dynein-dependent manner [19], and hindrance of MTOC polarization, molecular transport and cytoskeleton dynamics prevent proper propagation of TCR signals [20].It is now tempting to speculate that the localization of signalling modules within the IS may be instrumental for the formation of a Treg cell-specific IS and the suppressive phenotype of Treg cells. At this moment, however,...

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“…Physical contact between the Golgi and centriole is also required for cell polarization and movement when the Golgi and centriole move in unison to the leading edge of the cell. A striking example of the polarization of the Golgi/centriole complex is the formation of the immunological synapse between interacting immune cells during the immune response (Kloc et al 2014). Although we still do not fully understand the role of the association between the Golgi and centriole, it is believed that it facilitates polar/directional movement of the Golgi-derived secretory vesicles on the microtubules nucleated at the centrioles.…”

Section: Pericentriolar Location Of the Golgi Apparatusmentioning

confidence: 99%

RhoA Pathway and Actin Regulation of the Golgi/Centriole Complex

Kloc

Uosef

Wosik

et al. 2019

Results and Problems in Cell Differentiation

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In vertebrate cells, the Golgi apparatus is located in close proximity to the centriole. The architecture of the Golgi/centriole complex depends on a multitude of factors, including the actin filament cytoskeleton. In turn, both the Golgi and centriole act as the actin nucleation centers. Actin organization and polymerization also depends on the small GTPase RhoA pathway. In this chapter we summarize the most current knowledge on how the genetic, magnetic or pharmacologic interference with RhoA pathway and actin cytoskeleton directly or indirectly affects architecture, structure and function of Golgi/centriole complex.

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The newly found functions of MTOC in immunological response

Cited by 25 publications

References 151 publications

The Centrosome, a Multitalented Renaissance Organelle

The Centrosome, a Multitalented Renaissance Organelle

TCR signalling network organization at the immunological synapses of murine regulatory T cells

RhoA Pathway and Actin Regulation of the Golgi/Centriole Complex

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