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Disordered region of nuclear membrane protein Bqt4 recruits phosphatidic acid to the nuclear envelope to maintain its structural integrity
Journal of Biological Chemistry ( IF 4.0 ) Pub Date : 2024-05-31 , DOI: 10.1016/j.jbc.2024.107430
Yasuhiro Hirano , Tsukino Sato , Ayane Miura , Yoshino Kubota , Tomoko Shindo , Koichi Fukase , Tatsuo Fukagawa , Kazuya Kabayama , Tokuko Haraguchi , Yasushi Hiraoka

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 . The intrinsically disordered region (IDR) of Bqt4, proximal to the transmembrane domain, binds to PA and forms a solid aggregate . 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.

中文翻译:


核膜蛋白 Bqt4 的无序区域将磷脂酸募集至核膜以维持其结构完整性



核膜(NE)是一个可渗透的屏障,可维持核-细胞质区室化并确保核功能;然而,它会在机械应力和有丝分裂等各种情况下破裂。尽管用于密封破裂的 NE 的蛋白质成分已被鉴定,但脂质成分参与此过程的机制仍有待阐明。在这里,我们发现内核膜(INM)蛋白 Bqt4 直接与磷脂酸(PA)相互作用,并作为裂殖酵母中 NE 维持的平台。 Bqt4 的本质无序区域 (IDR) 靠近跨膜结构域,与 PA 结合并形成固体聚集体。 INM 中 Bqt4 IDR 的过度积累会导致细胞膜过度增殖和细胞核内脂滴形成,导致着丝粒与 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 招募到 INM 来控制核膜稳态,从而维持 NE 的结构完整性。
更新日期:2024-05-31
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