Rapid leukocyte migration by integrin-independent flowing and squeezing

Rapid leukocyte migration by integrin-independent flowing and squeezing
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DOI:
10.1038/nature06887
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发表时间:
2008-05-01
期刊:
影响因子:
64.8
通讯作者:
Sixt, Michael
Sixt, Michael
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Laemmermann, Tim;Bader, Bernhard L.;Sixt, Michael

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所有后生动物细胞都携带整合素家族的跨膜受体,其将肌动球蛋白细胞骨架的收缩力与细胞外环境偶联。与这一原理一致,快速迁移的白细胞在二维表面上移动时使用整合素介导的粘附.由于在二维基质上的迁移自然地过分强调粘附的作用,因此在组织内白细胞的三维运动期间整合素的贡献仍然存在争议。我们在体内和体外研究了间质白细胞趋化过程中粘附力、收缩力和膨胀力之间的相互作用。我们从鼠白细胞中清除了所有的整联蛋白异二聚体,并在这里显示功能性整联蛋白在三维环境中不有助于迁移。相反,这些细胞通过肌动蛋白网络扩张的唯一力量迁移,这促进了前缘的扩张流动。肌球蛋白II依赖性收缩仅在通过狭窄间隙时需要,其中后缘的挤压收缩推动刚性核。
All metazoan cells carry transmembrane receptors of the integrin family, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In agreement with this principle, rapidly migrating leukocytes use integrin- mediated adhesion when moving over two- dimensional surfaces. As migration on two- dimensional substrates naturally overemphasizes the role of adhesion, the contribution of integrins during three- dimensional movement of leukocytes within tissues has remained controversial. We studied the interplay between adhesive, contractile and protrusive forces during interstitial leukocyte chemotaxis in vivo and in vitro. We ablated all integrin heterodimers from murine leukocytes, and show here that functional integrins do not contribute to migration in three- dimensional environments. Instead, these cells migrate by the sole force of actin- network expansion, which promotes protrusive flowing of the leading edge. Myosin II- dependent contraction is only required on passage through narrow gaps, where a squeezing contraction of the trailing edge propels the rigid nucleus.