Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan.
J Biol Chem. 2024 Jul;300(7):107430. doi: 10.1016/j.jbc.2024.107430. Epub 2024 May 31.
The nuclear envelope (NE) is a permeable barrier that maintains nuclear-cytoplasmic compartmentalization and ensures nuclear function; however, it ruptures in various situations such as mechanical stress and mitosis. Although the protein components for sealing a ruptured NE have been identified, the mechanism by which lipid components are involved in this process remains to be elucidated. Here, we found that an inner nuclear membrane (INM) protein Bqt4 directly interacts with phosphatidic acid (PA) and serves as a platform for NE maintenance in the fission yeast Schizosaccharomyces pombe. The intrinsically disordered region (IDR) of Bqt4, proximal to the transmembrane domain, binds to PA and forms a solid aggregate in vitro. Excessive accumulation of Bqt4 IDR in INM results in membrane overproliferation and lipid droplet formation in the nucleus, leading to centromere dissociation from the NE and chromosome missegregation. Our findings suggest that Bqt4 IDR controls nuclear membrane homeostasis by recruiting PA to the INM, thereby maintaining the structural integrity of the NE.
核膜（NE）是一种具有通透性的屏障，它维持核质分隔并确保核功能；然而，在机械应激和有丝分裂等各种情况下，它会破裂。尽管已经确定了用于密封破裂的 NE 的蛋白质成分，但脂质成分如何参与这一过程的机制仍有待阐明。在这里，我们发现一种核内膜（INM）蛋白 Bqt4 直接与磷酸脂酸（PA）相互作用，并作为裂殖酵母 Schizosaccharomyces pombe 中维持 NE 的平台。Bqt4 的无规则结构域（IDR），靠近跨膜结构域，与 PA 结合，并在体外形成固体聚集体。INM 中 Bqt4 IDR 的过度积累导致核内膜过度增殖和脂滴形成，导致着丝粒从 NE 解离和染色体错误分离。我们的研究结果表明，Bqt4 IDR 通过将 PA 募集到 INM 来控制核膜动态平衡，从而维持 NE 的结构完整性。
