Torsin ATPases Influence Chromatin Interaction of the Torsin Regulator LAP1

Overview

Journal Elife

Specialty Biology

Date 2020 Dec 15

PMID 33320087

Citations 12

Authors

Naemi Luithle

Jelmi Uit de Bos

Ruud Hovius

Daria Maslennikova

Renard Tm Lewis

Rosemarie Ungricht

Beat Fierz

Ulrike Kutay

Affiliations

Soon will be listed here.

Abstract

The inner nuclear membrane is functionalized by diverse transmembrane proteins that associate with nuclear lamins and/or chromatin. When cells enter mitosis, membrane-chromatin contacts must be broken to allow for proper chromosome segregation; yet how this occurs remains ill-understood. Unexpectedly, we observed that an imbalance in the levels of the lamina-associated polypeptide 1 (LAP1), an activator of ER-resident Torsin AAA+-ATPases, causes a failure in membrane removal from mitotic chromatin, accompanied by chromosome segregation errors and changes in post-mitotic nuclear morphology. These defects are dependent on a hitherto unknown chromatin-binding region of LAP1 that we have delineated. LAP1-induced NE abnormalities are efficiently suppressed by expression of wild-type but not ATPase-deficient Torsins. Furthermore, a dominant-negative Torsin induces chromosome segregation defects in a LAP1-dependent manner. These results indicate that association of LAP1 with chromatin in the nucleus can be modulated by Torsins in the perinuclear space, shedding new light on the LAP1-Torsin interplay.

Citing Articles

LAP1 Interactome Profiling Provides New Insights into LAP1's Physiological Functions.

Pereira C, Espadas G, Martins F, Bertrand A, Servais L, Sabido E Int J Mol Sci. 2025; 25(24.

PMID: 39769001 PMC: 11678445. DOI: 10.3390/ijms252413235.

Quantitative proteome analysis of LAP1-deficient human fibroblasts: A pilot approach for predicting the signaling pathways deregulated in LAP1-associated diseases.

Pereira C, Espadas G, Martins F, Bertrand A, Servais L, Sabido E Biochem Biophys Rep. 2024; 39:101757.

PMID: 39035020 PMC: 11260385. DOI: 10.1016/j.bbrep.2024.101757.

Prognostic implications of TOR1B expression across cancer types: a focus on basal-like breast cancer and cellular adaptations to hypoxia.

Zhang Y, Cai Z, Chen W, Ye L, Wu X J Cancer Res Clin Oncol. 2024; 150(6):293.

PMID: 38842687 PMC: 11156733. DOI: 10.1007/s00432-024-05794-3.

Sculpting nuclear envelope identity from the endoplasmic reticulum during the cell cycle.

Deolal P, Scholz J, Ren K, Bragulat-Teixidor H, Otsuka S Nucleus. 2024; 15(1):2299632.

PMID: 38238284 PMC: 10802211. DOI: 10.1080/19491034.2023.2299632.

-Associated Nuclear Envelopathies.

Mackels L, Liu X, Bonne G, Servais L Int J Mol Sci. 2023; 24(8).

PMID: 37108075 PMC: 10138496. DOI: 10.3390/ijms24086911.

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