Drechsel D N, Hyman A A, Hall A, Glotzer M
MRC Laboratory for Molecular Cell Biology, University College, London WC1E 6BT, UK.
Curr Biol. 1997 Jan 1;7(1):12-23. doi: 10.1016/s0960-9822(06)00023-6.
During cytokinesis in animal cells, an equatorial actomyosin-based contractile ring divides the cell into two daughter cells. The position of the contractile ring is specified by a signal that emanates from the mitotic spindle. This signal has not been identified and it is not understood how the components of the contractile ring assemble. It is also unclear how the ring constricts or how new plasma membrane inserts specifically behind the leading edge of the constricting furrow. The Rho family of small GTPases regulate polarized changes in cell growth and cell shape by affecting the formation of actin structures beneath the plasma membrane, but their role in cytokinesis is unclear.
We have studied the function of two Rho family members during the early cell divisions of Xenopus embryos by injecting modified forms of Rho and Cdc42. Both inhibition and constitutive activation of either GTPase blocked cytokinesis. Furrow specification occurred normally, but ingression of the furrow was inhibited. Newly inserted cleavage membranes appeared aberrantly on the outer surface of the embryo. Microinjected Rho localized to the cortex and regulated the levels of cortical F-actin.
These results show that Rho regulates the assembly of actin filaments in the cortex during cytokinesis, that local activation of Rho is important for proper constriction of the contractile furrow, and that Cdc42 plays a role in furrow ingression. Moreover, our observations reveal that furrow ingression and membrane insertion are not strictly linked. Neither Rho nor Cdc42 appear to be required for establishment of the cell-division plane.
在动物细胞的胞质分裂过程中,基于肌动球蛋白的赤道收缩环将细胞分成两个子细胞。收缩环的位置由有丝分裂纺锤体发出的信号确定。该信号尚未被识别,并且不清楚收缩环的组件是如何组装的。同样不清楚环是如何收缩的,或者新的质膜是如何特异性地插入到收缩沟前缘后方的。小GTP酶的Rho家族通过影响质膜下方肌动蛋白结构的形成来调节细胞生长和细胞形状的极化变化,但其在胞质分裂中的作用尚不清楚。
我们通过注射修饰形式的Rho和Cdc42,研究了非洲爪蟾胚胎早期细胞分裂过程中两个Rho家族成员的功能。两种GTP酶的抑制和组成型激活均阻断了胞质分裂。沟的形成正常发生,但沟的内陷受到抑制。新插入的分裂膜异常出现在胚胎的外表面。显微注射的Rho定位于皮质并调节皮质F-肌动蛋白的水平。
这些结果表明,Rho在胞质分裂过程中调节皮质中肌动蛋白丝的组装,Rho的局部激活对于收缩沟的适当收缩很重要,并且Cdc42在沟的内陷中起作用。此外,我们的观察结果表明,沟的内陷和膜插入并不严格相关。细胞分裂平面的建立似乎既不需要Rho也不需要Cdc42。