Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
J Cell Biol. 2020 Sep 7;219(9). doi: 10.1083/jcb.201912117.
Pavarotti, the Drosophila MKLP1 orthologue, is a kinesin-like protein that works with Tumbleweed (MgcRacGAP) as the centralspindlin complex. This complex is essential for cytokinesis, where it helps to organize the contractile actomyosin ring at the equator of dividing cells by activating the RhoGEF Pebble. Actomyosin rings also function as the driving force during cell wound repair. We previously showed that Tumbleweed and Pebble are required for the cell wound repair process. Here, we show that Pavarotti also functions during wound repair and confirm that while Pavarotti, Tumbleweed, and Pebble are all used during this cellular repair, each has a unique localization pattern and knockdown phenotype, demonstrating centralspindlin-independent functions. Surprisingly, we find that the classically microtubule-associated Pavarotti binds directly to actin in vitro and in vivo and has a noncanonical role directly regulating actin dynamics. Finally, we demonstrate that this actin regulation by Pavarotti is not specific to cellular wound repair but is also used in normal development.
Pavarotti 是果蝇 MKLP1 的同源物，是一种驱动蛋白样蛋白，与 Tumbleweed（MgcRacGAP）一起作为中心纺锤体复合物发挥作用。该复合物对于胞质分裂是必不可少的，它通过激活 RhoGEF Pebble 帮助在分裂细胞的赤道处组织收缩性肌动球蛋白环。肌动球蛋白环也作为细胞伤口修复过程中的驱动力。我们之前表明 Tumbleweed 和 Pebble 是细胞伤口修复过程所必需的。在这里，我们表明 Pavarotti 在伤口修复过程中也发挥作用，并证实虽然 Pavarotti、Tumbleweed 和 Pebble 在这个细胞修复过程中都被使用，但每个都有独特的定位模式和敲低表型，表明中心纺锤体的非依赖性功能。令人惊讶的是，我们发现经典的微管相关 Pavarotti 在体外和体内直接与肌动蛋白结合，并具有直接调节肌动蛋白动力学的非典型作用。最后，我们证明 Pavarotti 的这种肌动蛋白调节不仅特定于细胞伤口修复，而且在正常发育中也被使用。
