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Reference - PMID:38825008 - Disordered region of nuclear membrane protein Bqt4 recruits phosphatidic acid to the nuclear envelope to maintain its structural integrity.

Reference summary

PubMed ID
PMID:38825008
Title
Disordered region of nuclear membrane protein Bqt4 recruits phosphatidic acid to the nuclear envelope to maintain its structural integrity.
Authors
Hirano Y, Sato T, Miura A, Kubota Y, Shindo T, Fukase K, Fukagawa T, Kabayama K, Haraguchi T, Hiraoka Y
Citation
J Biol Chem 2024 May 31;:107430
Publication year
2024
Abstract
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.

Annotation

GO biological process

GO:0071763 - nuclear membrane organization

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GO molecular function

GO:0070300 - phosphatidic acid binding

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Protein sequence feature

SO:0001534 - nuclear_rim_localization_signal

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Single locus phenotype

FYPO:0002338 - abnormal protein localization to nuclear periphery

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Genotypes:

FYPO:0006692 - cut with septum between unequally sized nuclei

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FYPO:0006800 - decreased centromere clustering at nuclear periphery during mitotic interphase

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FYPO:0001355 - decreased vegetative cell population growth

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FYPO:0001556 - excess nuclear envelope present

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FYPO:0007457 - excess nuclear envelope present during mitotic interphase

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FYPO:0008433 - increased inner nuclear membrane phosphatidic acid level

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0002360 - normal chromatin silencing at centromere

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FYPO:0004887 - normal protein localization to nuclear envelope during vegetative growth

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FYPO:0000703 - normal protein-protein interaction

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FYPO:0004924 - normal telomere tethering at nuclear periphery during vegetative growth

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FYPO:0008431 - nuclear lipid droplet formation

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FYPO:0000772 - perforated nuclear envelope

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FYPO:0002060 - viable vegetative cell population

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