Gibieža Paulius, Ratkevičiūtė Emilija, Dabkevičiūtė Girstautė, Petrikaitė Vilma
Laboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėlių Av. 13, 50162, Kaunas, Lithuania.
Biol Res. 2025 Aug 29;58(1):59. doi: 10.1186/s40659-025-00638-x.
Rab11 and Rab35 have been implicated in large-scale intracellular membrane trafficking during the last phases of the cell cycle. Although both proteins are associated with cytokinetic abscission, they appear to perform distinct functions and give rise to different phenotypes in dividing cells. Despite a substantial body of research on each protein individually, no study to date has systematically compared Rab11 and Rab35 in the context of cancer cell division. As a result, the extent of their interrelationship and potential compensatory mechanisms remains unclear. Our data demonstrate that Rab11a, Rab11b and Rab35 expression levels are partially interrelated. We also show that Rab11 and Rab35 contribute to mitotic progression in different ways, particularly during specific stages of the M-phase. Notably, depletion of either Rab11 or Rab35 disrupts cytokinetic abscission and correlates with aberrant F-actin accumulation at the intercellular bridge. Furthermore, overexpression of related Rab proteins with overlapping functions does not rescue the cytokinetic defects caused by Rab11 or Rab35 downregulation in cancer cells. Therefore, this study aims to deepen our understanding of how Rab11 and Rab35 orchestrate the molecular events that drive the progression from late anaphase through the completion of cytokinesis.
Rab11和Rab35在细胞周期的最后阶段参与大规模细胞内膜运输。尽管这两种蛋白都与胞质分裂切离有关，但它们似乎执行不同的功能，并在分裂细胞中产生不同的表型。尽管对每种蛋白都进行了大量的单独研究，但迄今为止，尚无研究在癌细胞分裂的背景下系统地比较Rab11和Rab35。因此，它们之间的相互关系程度和潜在的补偿机制仍不清楚。我们的数据表明，Rab11a、Rab11b和Rab35的表达水平部分相关。我们还表明，Rab11和Rab35以不同方式促进有丝分裂进程，特别是在M期的特定阶段。值得注意的是，Rab11或Rab35的缺失会破坏胞质分裂切离，并与细胞间桥处异常的F-肌动蛋白积累相关。此外，具有重叠功能的相关Rab蛋白的过表达并不能挽救癌细胞中Rab11或Rab35下调引起的胞质分裂缺陷。因此，本研究旨在加深我们对Rab11和Rab35如何协调从后期到胞质分裂完成所驱动的分子事件的理解。
