Ai Erkang, Poole Daniel S, Skop Ahna R
Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
Mol Biol Cell. 2009 Mar;20(6):1629-38. doi: 10.1091/mbc.e08-09-0917. Epub 2009 Jan 21.
Membrane trafficking pathways are necessary for the addition and removal of membrane during cytokinesis. In animal cells, recycling endosomes act as a major source of the additional membranes during furrow progression and abscission. However, the mechanisms and factors that regulate recycling endosomes during the cell cycle remain poorly understood. Here, we show that the Caenorhabditis elegans Receptor of Activated C Kinase 1 (RACK-1) is required for cytokinesis, germline membrane organization, and the recruitment of RAB-11-labeled recycling endosomes to the pericentrosomal region and spindle. RACK-1 is also required for proper chromosome separation and astral microtubule length. RACK-1 localizes to the centrosomes, kinetochores, the midbody, and nuclear envelopes during the cell cycle. We found that RACK-1 directly binds to DNC-2, the C. elegans p50/dynamitin subunit of the dynactin complex. Last, RACK-1 may facilitate the sequestration of recycling endosomes by targeting DNC-2 to centrosomes and the spindle. Our findings suggest a mechanism by which RACK-1 directs the dynactin-dependent redistribution of recycling endosomes during the cell cycle, thus ensuring proper membrane trafficking events during cytokinesis.
膜运输途径对于胞质分裂过程中膜的添加和去除是必需的。在动物细胞中,循环内体在沟的形成和脱离过程中作为额外膜的主要来源。然而,在细胞周期中调节循环内体的机制和因素仍知之甚少。在这里,我们表明秀丽隐杆线虫活化C激酶1受体(RACK-1)对于胞质分裂、生殖系膜组织以及将RAB-11标记的循环内体募集到中心体周围区域和纺锤体是必需的。RACK-1对于正确的染色体分离和星体微管长度也是必需的。在细胞周期中,RACK-1定位于中心体、动粒、中间体和核膜。我们发现RACK-1直接与DNC-2结合,DNC-2是动力蛋白激活复合物的秀丽隐杆线虫p50/动力蛋白亚基。最后,RACK-1可能通过将DNC-2靶向中心体和纺锤体来促进循环内体的隔离。我们的研究结果表明了一种机制,通过该机制RACK-1在细胞周期中指导动力蛋白依赖性的循环内体重分布,从而确保胞质分裂期间适当的膜运输事件。