Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240, USA.
J Cell Sci. 2024 Sep 15;137(18). doi: 10.1242/jcs.262347. Epub 2024 Sep 27.
Cytokinesis is the final stage of the cell cycle that results in the physical separation of daughter cells. To accomplish cytokinesis, many organisms build an actin- and myosin-based cytokinetic ring (CR) that is anchored to the plasma membrane (PM). Defects in CR-PM anchoring can arise when the PM lipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is depleted. In Schizosaccharomyces pombe, reduced PM PI(4,5)P2 results in a CR that cannot maintain a medial position and slides toward one cell end, resulting in two differently sized daughter cells. S. pombe PM PI(4,5)P2 is synthesized by the phosphatidylinositol 4-phosphate 5-kinase (PI5-kinase) Its3, but what regulates this enzyme to maintain appropriate PM PI(4,5)P2 levels in S. pombe is not known. To identify Its3 regulators, we used proximity-based biotinylation, and the uncharacterized protein Duc1 was specifically detected. We discovered that Duc1 decorates the PM except at the cell division site and that its unique localization pattern is dictated by binding to the endoplasmic reticulum (ER)-PM contact site proteins Scs2 and Scs22. Our evidence suggests that Duc1 also binds PI(4,5)P2 and helps enrich Its3 at the lateral PM, thereby promoting PM PI(4,5)P2 synthesis and robust CR-PM anchoring.
有丝分裂是细胞周期的最后一个阶段,导致子细胞的物理分离。为了完成胞质分裂,许多生物构建了一个由肌动蛋白和肌球蛋白组成的胞质分裂环(CR),该环锚定在质膜(PM)上。当质膜脂质磷脂酰肌醇(4,5)-双磷酸[PI(4,5)P2]耗尽时,CR-PM 锚定可能会出现缺陷。在酿酒酵母中,PM PI(4,5)P2 的减少导致 CR 无法保持中间位置并滑向一个细胞末端,从而导致两个大小不同的子细胞。S. pombe PM PI(4,5)P2 由磷脂酰肌醇 4-磷酸 5-激酶(PI5-kinase)Its3 合成,但什么调节这种酶以维持 S. pombe 中适当的 PM PI(4,5)P2 水平尚不清楚。为了鉴定 Its3 调节剂,我们使用了基于邻近的生物素化,并且未被表征的蛋白 Duc1 被特异性检测到。我们发现 Duc1 除了在细胞分裂部位外还装饰 PM,并且其独特的定位模式是由与内质网(ER)-PM 接触位点蛋白 Scs2 和 Scs22 结合决定的。我们的证据表明 Duc1 还结合 PI(4,5)P2 并帮助在侧向 PM 中富集 Its3,从而促进 PM PI(4,5)P2 合成和强大的 CR-PM 锚定。