T cell synapse assembly: proteins, motors and the underlying cell biology

Tooley, Aaron J.; Jacobelli, Jordan; Moldovan, Maria-Cristina; Douglas, Adam; Krummel, Matthew F.

doi:10.1016/j.smim.2004.09.006

Cited by 13 publications

(9 citation statements)

References 45 publications

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“…It has been suggested that an active actin-based process aids in moving proteins across the membrane (14)(15)(16). Based on this hypothesis, some groups have looked for the role of lymphocyte myosins such as MyH9/NMMHC-IIA in the reorganization of membrane receptors, like TCR, during IS formation.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that an active actin-dependent process is responsible for moving or anchoring certain membrane proteins to defined locations (14,15). Because myosins are the primary microfilamentassociated motors, they represent likely candidates to mediate this function (16). In lymphocytes, myosin II has been reported to participate in IS formation, but not necessarily to contribute to polarization of signaling proteins to the synapse interface (4,5).…”

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confidence: 99%

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Myosin 1c Participates in B Cell Cytoskeleton Rearrangements, Is Recruited to the Immunologic Synapse, and Contributes to Antigen Presentation

Maravillas-Montero

Gillespie

Patiño-López

et al. 2011

The Journal of Immunology

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Myosin 1c (Myo1c) is a member of the unconventional class I myosins of vertebrates, which directly link the plasma membrane with the microfilament cortical web. Although this molecular motor has been implicated in cell functions such as cytoskeleton organization, cell motility, nuclear transcription, and endocytosis, its role in hematopoietic cells is largely unknown. In this study, we show that Myo1c is abundantly expressed in murine B lymphocytes and is preferentially located at the plasma membrane, especially in peripheral processes such as microvilli. We observed that this motor concentrates at the growing membrane protrusions generated during B cell spreading and that it is actively recruited to the immune synapse. Interestingly, Myo1c was detected in lipid rafts of B cells and showed strong colocalization with MHC-II, particularly after cross-linking of these molecules. By transfection of a dominant negative form of Myo1c or specific siRNA, we also detected alterations in the spreading and Ag-presenting ability of these cells. The data suggest that Myo1c is involved in the cytoskeleton dynamics and membrane protein anchoring or sorting in B lymphocytes.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Myosin 1c Participates in B Cell Cytoskeleton Rearrangements, Is Recruited to the Immunologic Synapse, and Contributes to Antigen Presentation

Maravillas-Montero

Gillespie

Patiño-López

et al. 2011

The Journal of Immunology

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“…These initial studies attributed these effects to changes in the plasma membrane lipid composition. More recent investigations, however, using pharmacological agents that inhibit F-actin polymerization, such as lantrunculin and cytochalasin, have shown that decreases in F-actin polymerization can increase T cell membrane fluidity (Doherty and McMahon, 2008; Tooley et al, 2005; Blanchard and Hivroz, 2002a; Sheetz, 1993; Heath and Holifield, 1991; Groves, 2005; Blanchard and Hivroz, 2002b; de Pablo and varez de, 2000). This observation raises the possibility that increases in F-actin polymerization with age could be responsible for the decrease in membrane fluidity seen in T cells from old donors.…”

Section: A) Age-related Defects In the T Cell Receptor Signaling Pathmentioning

confidence: 99%

Age-related defects in the cytoskeleton signaling pathways of CD4 T cells

Garcia¹,

Miller²

2011

Ageing Research Reviews

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SummaryIt has been postulated that the cytoskeleton controls many aspects of T cell function, including activation, proliferation and apoptosis. Recent advances in our understanding of F-actin polymerization and the Ezrin-Radixin-Moesin (ERM) family of cytoskeleton signal proteins have provided new insights into immunological synapse formation during T cell activation. During aging there is a significant decline of T cell function largely attributable to declines in activation of CD4 T cells and defects in the formation of the immunological synapse. Here we discuss recent progress in the understanding of how aging alters F-actin and ERM proteins in mouse CD4 T cells, and the implications of these changes for the T cell activation process.

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“…Second, the formation of an immunologic synapse must occur. The formation of the immunologic synapse can be visualized with microscopy as a 3-dimensional tripleringed structure called the supramolecular activation complex (SMAC) [40]. The SMAC is formed due to changes in the actin cytoskeletons of the T cell and APC and has been shown to contain TCRs, MHC-antigen complexes, the CD4 and CD8 coreceptors, and enzyme-bearing plasma membrane lipid rafts, all of which are required for T cell activation [41].…”

Section: Signal 1: Antigen Presentation To the T Cellsmentioning

confidence: 99%

Costimulation, Coinhibition and Cancer

Inman

Frigola

Dong³

et al. 2007

CCDT

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The immune system is an important defense mechanism against cancer and is often dysfunctional in patients with malignancies. The central regulator of the anti-cancer adaptive immune response is the T lymphocyte. T lymphocyte activation requires the completion of a carefully orchestrated series of specific steps that can be preempted or disrupted by any number of critical events. Particularly important is the provision of a costimulatory signal, the binding of accessory molecules on the antigen presenting cell to receptors on the T lymphocyte. Though costimulatory signals were traditionally envisioned as T lymphocyte-activating events, recent discoveries have highlighted their duality: they can be either stimulatory (costimulation) or inhibitory (coinhibition). In this article we review costimulation and coinhibition as potential targets for cancer therapy. We begin by presenting a general framework for thinking about the immune system in the context of cancer. Our discussion then bridges the various aspects of immune dysfunction seen in cancer with the presence of coinhibitory (ex: PD-1, PD-L1, CTLA-4, BTLA) and costimulatory (ex: CD28, ICOS, 4-1BB, CD40, OX40, CD27) signaling. Lastly, we develop a model of cancer-related immune dysfunction that parallels the concept of immunoediting. Throughout the article we emphasize clinically relevant research often applicable-but not limited-to the example of renal cell carcinoma.

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T cell synapse assembly: proteins, motors and the underlying cell biology

Cited by 13 publications

References 45 publications

Myosin 1c Participates in B Cell Cytoskeleton Rearrangements, Is Recruited to the Immunologic Synapse, and Contributes to Antigen Presentation

Myosin 1c Participates in B Cell Cytoskeleton Rearrangements, Is Recruited to the Immunologic Synapse, and Contributes to Antigen Presentation

Age-related defects in the cytoskeleton signaling pathways of CD4 T cells

Costimulation, Coinhibition and Cancer

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