LCCB, Center for Genetics and Development, University of California at Davis, Davis, CA 95616, USA.
J Cell Sci. 2010 Jun 1;123(Pt 11):1862-72. doi: 10.1242/jcs.064048. Epub 2010 May 4.
We investigated the role of Pav-KLP, a kinesin-6, in the coordination of spindle and cortical dynamics during mitosis in Drosophila embryos. In vitro, Pav-KLP behaves as a dimer. In vivo, it localizes to mitotic spindles and furrows. Inhibition of Pav-KLP causes defects in both spindle dynamics and furrow ingression, as well as causing changes in the distribution of actin and vesicles. Thus, Pav-KLP stabilizes the spindle by crosslinking interpolar microtubule bundles and contributes to actin furrow formation possibly by transporting membrane vesicles, actin and/or actin regulatory molecules along astral microtubules. Modeling suggests that furrow ingression during cellularization depends on: (1) a Pav-KLP-dependent force driving an initial slow stage of ingression; and (2) the subsequent Pav-KLP-driven transport of actin- and membrane-containing vesicles to the furrow during a fast stage of ingression. We hypothesize that Pav-KLP is a multifunctional mitotic motor that contributes both to bundling of interpolar microtubules, thus stabilizing the spindle, and to a biphasic mechanism of furrow ingression by pulling down the furrow and transporting vesicles that deliver new material to the descending furrow.
我们研究了驱动蛋白-6 家族成员 Pav-KLP 在果蝇胚胎有丝分裂过程中纺锤体和皮质动力学协调中的作用。体外实验表明,Pav-KLP 表现为二聚体。在体内,它定位于有丝分裂纺锤体和凹陷处。Pav-KLP 的抑制导致纺锤体动力学和凹陷内陷缺陷,以及肌动蛋白和囊泡分布的变化。因此,Pav-KLP 通过交联两极微管束稳定纺锤体,并可能通过沿星体微管运输膜囊泡、肌动蛋白和/或肌动蛋白调节分子来促进肌动蛋白形成凹陷。建模表明,细胞化过程中的凹陷内陷取决于:(1)Pav-KLP 依赖性力驱动初始缓慢的内陷阶段;(2)随后在快速内陷阶段,Pav-KLP 驱动含有肌动蛋白和膜的囊泡向凹陷处运输。我们假设 Pav-KLP 是一种多功能的有丝分裂马达,它不仅有助于两极微管的束集,从而稳定纺锤体,而且还通过拉动凹陷和运输将新材料输送到下降凹陷的囊泡来参与凹陷内陷的双相机制。