Mitochondrial and plasma membrane pools of stomatin-like protein 2 coalesce at the immunological synapse during T cell activation.
Mitochondrial and plasma membrane pools of stomatin-like protein 2 coalesce at the immunological synapse during T cell activation.
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DOI：
10.1371/journal.pone.0037144
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Madrenas J
中科院分区：
文献类型：
--
作者：
Christie DA;Kirchhof MG;Vardhana S;Dustin ML;Madrenas J
Stomatin 样蛋白 2 (SLP-2) 是 Stomatin – 抑制素 – flotillin – HflC/K (SPFH) 超家族的成员。最近的证据表明，SLP-2 参与线粒体膜中富含心磷脂的微结构域的组织以及线粒体生物合成和功能的调节。在 T 细胞中，这种作用转化为增强的 T 细胞激活。尽管 SLP-2 的主要库与线粒体相关，但我们在此表明还有一个与 T 细胞质膜相关的 SLP-2 库。 T 细胞激活后，质膜相关和线粒体相关的 SLP-2 库都会在免疫突触 (IS) 处合并。 IS 的形成和线粒体重新定位到 IS 都不需要 SLP-2，因为 SLP-2 缺陷的 T 细胞在响应 T 细胞激活时表现出这些细胞器的正常重新定位。有趣的是，在 T 细胞激活后，我们发现 SLP-2 的表面池大部分被排除在中央超分子激活复合物之外，并在信号传导 TCR 微簇所在的 IS 外围区域富集。基于这些结果，我们提出 SLP-2 不仅促进线粒体膜的区室化，而且还促进质膜的区室化进入功能性微域。在后一个位置，SLP-2 可能促进 TCR 信号体成分的最佳组装。我们的数据还表明，线粒体和质膜之间可能存在膜材料的净交换，这解释了质膜中某些线粒体蛋白的存在。
Stomatin-like protein 2 (SLP-2) is a member of the stomatin – prohibitin – flotillin – HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane.
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DOI：
10.4049/jimmunol.181.3.1927
发表时间：
2008-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kirchhof MG;Chau LA;Lemke CD;Vardhana S;Darlington PJ;Márquez ME;Taylor R;Rizkalla K;Blanca I;Dustin ML;Madrenas J
通讯作者：
Madrenas J
影响因子：
56.9
作者：
Lee, KH;Holdorf, AD;Shaw, AS
通讯作者：
Shaw, AS
影响因子：
9.2
作者：
Braschi, Emelie;Goyon, Vanessa;McBride, Heidi M.
通讯作者：
McBride, Heidi M.
影响因子：
56.9
作者：
Lee, KH;Dinner, AR;Shaw, AS
通讯作者：
Shaw, AS
影响因子：
5.3
作者：
Arp, J;Kirchhof, MG;Madrenas, J
通讯作者：
Madrenas, J