Eddy Robert J, Pierini Lynda M, Maxfield Frederick R
Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.
Mol Biol Cell. 2002 Dec;13(12):4470-83. doi: 10.1091/mbc.e02-04-0241.
The development of cell polarity in response to chemoattractant stimulation in human polymorphonuclear neutrophils (PMNs) is characterized by the rapid conversion from round to polarized morphology with a leading lamellipod at the front and a uropod at the rear. During PMN polarization, the microtubule (MT) array undergoes a dramatic reorientation toward the uropod that is maintained during motility and does not require large-scale MT disassembly or cell adhesion to the substratum. MTs are excluded from the leading lamella during polarization and motility, but treatment with a myosin light chain kinase inhibitor (ML-7) or the actin-disrupting drug cytochalasin D causes an expansion of the MT array and penetration of MTs into the lamellipod. Depolymerization of the MT array before stimulation caused 10% of the cells to lose their polarity by extending two opposing lateral lamellipodia. These multipolar cells showed altered localization of a leading lamella-specific marker, talin, and a uropod-specific marker, CD44. In summary, these results indicate that F-actin- and myosin II-dependent forces lead to the development and maintenance of MT asymmetry that may act to reinforce cell polarity during PMN migration.
人类多形核中性粒细胞（PMN）对趋化因子刺激作出反应时细胞极性的发展，其特征是从圆形迅速转变为极化形态，前端有一个领先的片状伪足，后端有一个尾足。在PMN极化过程中，微管（MT）阵列会发生显著的重新定向，朝向尾足，这种定向在细胞运动过程中得以维持，且不需要大规模的MT解聚或细胞与基质的粘附。在极化和运动过程中，MT被排除在领先的片状伪足之外，但用肌球蛋白轻链激酶抑制剂（ML-7）或破坏肌动蛋白的药物细胞松弛素D处理会导致MT阵列扩展并使MT渗透到片状伪足中。刺激前MT阵列的解聚导致10%的细胞通过延伸两个相对的横向片状伪足而失去极性。这些多极细胞显示领先片状伪足特异性标记物踝蛋白和尾足特异性标记物CD44的定位发生了改变。总之，这些结果表明，F-肌动蛋白和肌球蛋白II依赖性力量导致MT不对称的发展和维持，这可能在PMN迁移过程中起到加强细胞极性的作用。
