MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1–IRF3 signaling axis

Seo, Minji; Lee, Seong-Ok; Kim, Jihoon; Hong, Yujin; Kim, Seongchan; Kim, Yeumin; Min, Dal‐Hee; Kong, Young‐Yun; Shin, Jin‐Wook; Ahn, Kwangseog

doi:10.1073/pnas.1615287113

Cited by 31 publications

(28 citation statements)

References 25 publications

(29 reference statements)

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“…Whereas the role of dynein as force generator in centrosome translocation in T cells is firmly established, little is known about the properties of the MT network and MT dynamics that facilitate this rapid cytoskeletal reorganization, and only a few MT regulators participating in this process have been identified. Among them, MT-associated protein MAP4 was shown to be required for centrosome translocation (Bustos-Moran et al, 2017), potentially due its ability to regulate dynein (Samora et al, 2011;Semenova et al, 2014;Seo et al, 2016). In addition, both acetylation and detyrosination of MTs and a complex of casein kinase Iδ with EB1 were suggested to be important for efficient centrosome polarization (Andres-Delgado et al, 2012;Serrador et al, 2004;Zyss et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

Hooikaas

Damstra

Gros

et al. 2020

Preprint

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When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome towards the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule dynamics contributes to this process. Here, we show that the knockout of KIF21B, a kinesin-4 linked to autoimmune disorders, causes microtubule overgrowth and perturbs centrosome translocation. KIF21B restricts microtubule length by inducing microtubule pausing typically followed by catastrophe. Catastrophe induction with vinblastine prevented microtubule overgrowth and was sufficient to rescue centrosome polarization in KIF21B-knockout cells. Biophysical simulations showed that a relatively small number of KIF21B molecules can restrict microtubule length and promote an imbalance of dynein-mediated pulling forces that allows the centrosome to translocate past the nucleus. We conclude that proper control of microtubule length is important for allowing rapid remodeling of the cytoskeleton and efficient T cell polarization.

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Section: Introductionmentioning

confidence: 99%

Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

Hooikaas

Damstra

Gros

et al. 2020

Preprint

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“…HSV-1 (a gift from J. H. Ahn; Sungkyunkwan University, Suwon, Republic of Korea) was prepared and used as previously described (57). For plaque assay, HFF cells were inoculated with serial dilutions of viruses and incubated with methyl cellulose overlay.…”

Section: Methodsmentioning

confidence: 99%

Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state

Song

Lee

Cho

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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RNA represents a pivotal component of host–pathogen interactions. Human cytomegalovirus (HCMV) infection causes extensive alteration in host RNA metabolism, but the functional relationship between the virus and cellular RNA processing remains largely unknown. Through loss-of-function screening, we show that HCMV requires multiple RNA-processing machineries for efficient viral lytic production. In particular, the cellular RNA-binding protein Roquin, whose expression is actively stimulated by HCMV, plays an essential role in inhibiting the innate immune response. Transcriptome profiling revealed Roquin-dependent global down-regulation of proinflammatory cytokines and antiviral genes in HCMV-infected cells. Furthermore, using cross-linking immunoprecipitation (CLIP)-sequencing (seq), we identified IFN regulatory factor 1 (IRF1), a master transcriptional activator of immune responses, as a Roquin target gene. Roquin reduces IRF1 expression by directly binding to its mRNA, thereby enabling suppression of a variety of antiviral genes. This study demonstrates how HCMV exploits host RNA-binding protein to prevent a cellular antiviral response and offers mechanistic insight into the potential development of CMV therapeutics.

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“…These data suggested that BTN3A subfamily could enhance and amplify inflammatory signals that are initiated by other receptors. On THP-1 cells [human monocytic cell line derived from acute myeloid leukemia (AML) patient], depletion of BTN3A1 inhibited the cytoplasmic nucleic acid- or virus-triggered activation of IFN-β production, suggesting that BTN3A1 may be a novel regulator of type I IFN responses ( 61 ).…”

Section: Focus On Btn3a Role On the Activation Process Of Human Vγ9vδmentioning

confidence: 99%

New Insights Into the Regulation of γδ T Cells by BTN3A and Other BTN/BTNL in Tumor Immunity

Blazquez

Benyamine

Pasero³

et al. 2018

Front. Immunol.

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Recent findings in the immunology field have pointed out the emergent role of butyrophilins/butyrophilin-like molecules (BTN/BTNL in human, Btn/Btnl in mouse) in the modulation of γδ T cells. As long as the field develops exponentially, new relationships between certain γδ T cell subsets, on one hand, and their BTN/BTNL counterparts mainly present on epithelial and tumor cells, on the other, are described in the scientific literature. Btnl1/Btnl6 in mice and BTNL3/BTNL8 in humans regulate the homing and maturation of Vγ7+ and Vγ4+ T cells to the gut epithelium. Similarly, Skint-1 has shown to shape the dendritic epidermal T cells repertoire and their activation levels in mice. We and others have identified BTN3A proteins are the key mediators of phosphoantigen sensing by human Vγ9Vδ2 T cells. Here, we first synthesize the modulation of specific γδ T cell subsets by related BTN/BTNL molecules, in human and mice. Then, we focus on the role of BTN3A in the activation of Vγ9Vδ2 T cells, and we highlight the recent advances in the understanding of the expression, regulation, and function of BTN3A in tumor immunity. Hence, recent studies demonstrated that several signals induced by cancer cells or their microenvironment can regulate the expression of BTN3A. Moreover, antibodies targeting BTN3A have shown in vitro and in vivo efficacy in human tumors such as acute myeloid leukemia or pancreatic cancer. We thus finally discuss how these findings could help develop novel γδ T cell-based immunotherapeutical approaches.

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MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1–IRF3 signaling axis

Cited by 31 publications

References 25 publications

Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state

New Insights Into the Regulation of γδ T Cells by BTN3A and Other BTN/BTNL in Tumor Immunity

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