Glover David M, Capalbo Luisa, D'Avino Pier Paolo, Gatt Melanie K, Savoian Matthew S, Takeda Tetsuya
Cancer Research U.K. Cell Cycle Genetics Research Group, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH, UK.
Biochem Soc Trans. 2008 Jun;36(Pt 3):400-4. doi: 10.1042/BST0360400.
Microtubules maintain an intimate relationship with the rings of anillin, septins and actomyosin filaments throughout cytokinesis. In Drosophila, peripheral microtubules emanating from the spindle poles contact the equatorial cell cortex to deliver the signal that initiates formation of the cytokinetic furrow. Mutations that affect microtubule stability lead to ectopic furrowing because peripheral microtubules contact inappropriate cortical sites. The PAV-KLP (Pavarotti-kinesin-like protein)/RacGAP50C (where GAP is GTPase-activating protein) centralspindlin complex moves towards the plus ends of microtubules to reach the cell equator. When RacGAP50C is tethered to the cell membrane, furrowing initiates at multiple non-equatorial sites, indicating that mis-localization of this single molecule is sufficient to promote furrowing. Furrow formation and ingression requires RhoA activation by the RhoGEF (guanine-nucleotide-exchange factor) Pebble, which interacts with RacGAP50C. RacGAP50C also binds anillin, which associates with actin, myosin and septins. Thus RacGAP50C plays a pivotal role during furrow formation by activating RhoA and linking the peripheral microtubules with the nascent rings through its interaction with anillin.
在整个胞质分裂过程中，微管与肌动蛋白结合蛋白、隔膜蛋白和肌动球蛋白丝的环保持密切关系。在果蝇中，从纺锤极发出的外周微管与赤道细胞皮层接触，传递启动胞质分裂沟形成的信号。影响微管稳定性的突变会导致异位沟的形成，因为外周微管接触到了不适当的皮层位点。PAV-KLP（类帕瓦罗蒂驱动蛋白）/RacGAP50C（其中GAP是GTP酶激活蛋白）中心纺锤体复合物向微管的正端移动，以到达细胞赤道。当RacGAP50C被拴系到细胞膜上时，沟在多个非赤道位点开始形成，这表明该单一分子的错误定位足以促进沟的形成。沟的形成和内陷需要由RhoGEF（鸟嘌呤核苷酸交换因子）卵石激活RhoA，卵石与RacGAP50C相互作用。RacGAP50C还结合肌动蛋白结合蛋白，后者与肌动蛋白、肌球蛋白和隔膜蛋白相关联。因此，RacGAP50C在沟形成过程中通过激活RhoA并通过其与肌动蛋白结合蛋白的相互作用将外周微管与新生环连接起来，发挥着关键作用。
