ARHGAP45 controls naïve T- and B-cell entry into lymph nodes and T-cell progenitor thymus seeding.
ARHGAP45 controls naïve T- and B-cell entry into lymph nodes and T-cell progenitor thymus seeding.
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ARHGAP45 控制幼稚 T 细胞和 B 细胞进入淋巴结和 T 细胞祖胸腺播种
DOI：
10.15252/embr.202052196
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发表时间：
2021-04-07
期刊：
影响因子：
7.7
通讯作者：
Malissen B
中科院分区：
文献类型：
--
作者：
He L;Valignat MP;Zhang L;Gelard L;Zhang F;Le Guen V;Audebert S;Camoin L;Fossum E;Bogen B;Wang H;Henri S;Roncagalli R;Theodoly O;Liang Y;Malissen M;Malissen B
T和B细胞在血液和次级淋巴器官之间不断地再循环。为了促进其跨内皮迁移（TEM），趋化因子受体部分通过GTP酶激活蛋白（GAP）控制RHO家族小GTP酶的活性。T和B细胞表达几种RHO-GAP，其中大部分的功能仍然未知。ARHGAP 45 GAP主要在造血细胞中表达。为了定义其体内功能，我们描述了两种小鼠模型，其中ARHGAP 45在T细胞中被全身性或选择性地消融。我们联合收割机其分析与亲和纯化结合质谱法，以确定T细胞中的ARHGAP 45相互作用组，并与时间推移和反射干涉对比显微镜相结合，以评估ARGGAP 45在T细胞极化和运动中的作用。我们证明了ARHGAP 45调节幼稚T细胞的变形性和运动性。在生理条件下，ARHGAP 45控制幼稚T和B细胞进入淋巴结，而在竞争性再增殖下，它进一步调节骨髓中的造血祖细胞植入和T细胞祖细胞胸腺接种。因此，ARGHAP 45 GAP控制T和B细胞生命中的多个关键步骤。T和B细胞在血液和次级淋巴器官之间不断地再循环。RHO GT3活化蛋白ARHGAP 45调节幼稚T细胞的变形性、运动性和趋化性，从而调节体内T和B细胞的关键运输步骤。
T and B cells continually recirculate between blood and secondary lymphoid organs. To promote their trans‐endothelial migration (TEM), chemokine receptors control the activity of RHO family small GTPases in part via GTPase‐activating proteins (GAPs). T and B cells express several RHO‐GAPs, the function of most of which remains unknown. The ARHGAP45 GAP is predominantly expressed in hematopoietic cells. To define its in vivo function, we describe two mouse models where ARHGAP45 is ablated systemically or selectively in T cells. We combine their analysis with affinity purification coupled to mass spectrometry to determine the ARHGAP45 interactome in T cells and with time‐lapse and reflection interference contrast microscopy to assess the role of ARGHAP45 in T‐cell polarization and motility. We demonstrate that ARHGAP45 regulates naïve T‐cell deformability and motility. Under physiological conditions, ARHGAP45 controls the entry of naïve T and B cells into lymph nodes whereas under competitive repopulation it further regulates hematopoietic progenitor cell engraftment in the bone marrow, and T‐cell progenitor thymus seeding. Therefore, the ARGHAP45 GAP controls multiple key steps in the life of T and B cells. T and B cells continually recirculate between blood and secondary lymphoid organs. The RHO GTPase activating protein ARHGAP45 regulates naïve T cell deformability, motility, and chemotaxis, and thereby regulates key trafficking steps of T and B cells in vivo.
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DOI：
10.1083/jcb.201612069
发表时间：
2018-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lawson CD;Ridley AJ
通讯作者：
Ridley AJ
影响因子：
32.4
作者：
Cordeiro Gomes A;Hara T;Lim VY;Herndler-Brandstetter D;Nevius E;Sugiyama T;Tani-Ichi S;Schlenner S;Richie E;Rodewald HR;Flavell RA;Nagasawa T;Ikuta K;Pereira JP
通讯作者：
Pereira JP
影响因子：
3.7
作者：
de Kreuk BJ;Schaefer A;Anthony EC;Tol S;Fernandez-Borja M;Geerts D;Pool J;Hambach L;Goulmy E;Hordijk PL
通讯作者：
Hordijk PL
影响因子：
4
作者：
Amado-Azevedo, J.;Reinhard, N. R.;Hordijk, P. L.
通讯作者：
Hordijk, P. L.
影响因子：
9.9
作者：
Locard-Paulet, Marie;Voisinne, Guillaume;Roncagalli, Romain
通讯作者：
Roncagalli, Romain