Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration.
Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration.
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DOI：
10.1084/jem.20071543
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发表时间：
2008-01-21
期刊：
影响因子：
--
通讯作者：
Kim M
中科院分区：
文献类型：
--
作者：
Morin NA;Oakes PW;Hyun YM;Lee D;Chin YE;King MR;Springer TA;Shimaoka M;Tang JX;Reichner JS;Kim M
精确的细胞黏附和去黏附的时空调控是淋巴细胞动态迁移的关键。虽然关于整合素淋巴细胞功能相关抗原-1(LFA-1)黏附的信息已经很多，但在T淋巴细胞迁移过程中，调节细胞间黏附分子-1(ICAM-1)有效地解粘LFA-1的机制尚不清楚。在这里，我们发现非肌肉肌球蛋白重链IIA(Myh9)被募集到迁移中的T淋巴细胞的尾足部的LFA-1上，抑制Myh9与LFA-1的结合会导致尾部极端延长、尾部脱落缺陷和淋巴细胞在ICAM-1上的迁移减少，而不影响趋化因子CXCL-12对LFA-1的激活。这一缺陷可被同时抑制LFA-1亲和力和亲和力调节的小分子拮抗剂逆转，但不能被仅抑制亲和力调节的拮抗剂逆转。迁移T淋巴细胞与ICAM-1底物接触区的全内反射荧光显微镜显示，非活性LFA-1选择性地定位于极化T淋巴细胞的后部，而活性LFA-1则定位于其前部。因此，在T淋巴细胞迁移过程中，尿足细胞的黏附取决于LFA-1的亲和力，其中Myh9是LFA-1和细胞骨架之间的关键机械连接，细胞骨架是LFA-1去黏附的关键。
Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function–associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion.
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影响因子：
56.9
作者：
Campbell, JJ;Hedrick, J;Butcher, EC
通讯作者：
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32.4
作者：
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DOI：
10.1083/jcb.200404160
发表时间：
2004-12-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Springer TA
影响因子：
30.5
作者：
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