通过不依赖整合素的流动和挤压实现快速白细胞迁移。
Rapid leukocyte migration by integrin-independent flowing and squeezing.
作者信息
Lämmermann Tim, Bader Bernhard L, Monkley Susan J, Worbs Tim, Wedlich-Söldner Roland, Hirsch Karin, Keller Markus, Förster Reinhold, Critchley David R, Fässler Reinhard, Sixt Michael
机构信息
Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
出版信息
Nature. 2008 May 1;453(7191):51-5. doi: 10.1038/nature06887.
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.
所有后生动物细胞都携带整合素家族的跨膜受体,这些受体将肌动球蛋白细胞骨架的收缩力与细胞外环境联系起来。根据这一原理,快速迁移的白细胞在二维表面移动时利用整合素介导的黏附作用。由于在二维底物上的迁移自然会过度强调黏附的作用,整合素在白细胞在组织内的三维运动过程中的作用一直存在争议。我们研究了体内和体外间质白细胞趋化过程中黏附力、收缩力和突出力之间的相互作用。我们从鼠类白细胞中去除了所有整合素异二聚体,并在此表明功能性整合素对三维环境中的迁移没有贡献。相反,这些细胞仅通过肌动蛋白网络扩张的力量迁移,这促进了前缘的突出流动。只有在穿过狭窄间隙时才需要肌球蛋白II依赖性收缩,在狭窄间隙处后缘的挤压收缩推动刚性细胞核。