Desterke Christophe, Gassama-Diagne Ama
Université Paris-Sud, UFR Medecine- INSERM UMS33, Villejuif, France.
INSERM, Unité 1193, Villejuif, F-94800, France; Université Paris-Sud, UMR-S 1193, Villejuif, F-94800, France.
Adv Biol Regul. 2019 Aug;73:100635. doi: 10.1016/j.jbior.2019.100635. Epub 2019 Jul 27.
Septins are a family of GTP-binding proteins that assemble into non-polar filaments which can be recruited to negatively charged membranes and serve as a scaffold to recruit cytosolic proteins and cytoskeletal elements such as microtubules and actin so that they can perform their important biological functions. Human septins consist of four groups, each with 13 members, and filaments formation usually involve members from each group in specific positions. However, little is known about the molecular mechanisms that drive the binding of septins to membranes and its importance to their biological functions. Here we have built a protein-protein interaction (PPI) network around human septins and highlighted the connections with 170 partners. Functional enrichment by inference of the network of septins and their partners revealed their participation in functions consistent with some of the roles described for septins, including cell cycle, cell division and cell shape, but we also identified septin partners in these functions that had not previously been described. Interestingly, we identified important and multiple connections between septins and mRNA processing and their export from the nucleus. Analysis of the enrichment of gene ontology cellular components highlighted some important interactions between molecules involved in the spliceosome with septin 2 and septin 7 in particular. RNA splicing regulates gene expression, and through it, cell fate, development and physiology. Mutations in components of the in the splicing machinery is linked to several diseases including cancer, thus taken together, the different analyses presented here open new perspectives to elucidate the pathobiological role of septins.
Septin蛋白家族是一类GTP结合蛋白，它们组装成非极性细丝，可被募集到带负电荷的膜上，并作为支架募集胞质蛋白和细胞骨架成分，如微管和肌动蛋白，从而使它们能够发挥重要的生物学功能。人类Septin蛋白分为四组，每组有13个成员，细丝的形成通常涉及每组中特定位置的成员。然而，对于驱动Septin蛋白与膜结合的分子机制及其对其生物学功能的重要性知之甚少。在这里，我们围绕人类Septin蛋白构建了一个蛋白质-蛋白质相互作用（PPI）网络，并突出了与170个伙伴的联系。通过对Septin蛋白及其伙伴网络的推断进行功能富集分析，揭示了它们参与了与Septin蛋白所描述的一些作用一致的功能，包括细胞周期、细胞分裂和细胞形状，但我们也在这些功能中鉴定出了以前未描述过的Septin蛋白伙伴。有趣的是，我们发现了Septin蛋白与mRNA加工及其从细胞核输出之间的重要且多重联系。基因本体细胞成分的富集分析突出了剪接体中涉及的分子之间的一些重要相互作用，特别是与Septin 2和Septin 7之间的相互作用。RNA剪接调节基因表达，并通过它调节细胞命运、发育和生理功能。剪接机制成分的突变与包括癌症在内的几种疾病有关，因此，这里提出的不同分析为阐明Septin蛋白的病理生物学作用开辟了新的视角。
