» Articles » PMID: 37162852

TorsinA is Essential for the Timing and Localization of Neuronal Nuclear Pore Complex Biogenesis

Overview
Journal bioRxiv
Date 2023 May 10
PMID 37162852
Authors
Affiliations
Soon will be listed here.
Abstract

Nuclear pore complexes (NPCs) regulate information transfer between the nucleus and cytoplasm. NPC defects are linked to several neurological diseases, but the processes governing NPC biogenesis and spatial organization are poorly understood. Here, we identify a temporal window of strongly upregulated NPC biogenesis during neuronal maturation. We demonstrate that the AAA+ protein torsinA, whose loss of function causes the neurodevelopmental movement disorder DYT-TOR1A (DYT1) dystonia, coordinates NPC spatial organization during this period without impacting total NPC density. Using a new mouse line in which endogenous Nup107 is Halo-Tagged, we find that torsinA is essential for correct localization of NPC formation. In the absence of torsinA, the inner nuclear membrane buds excessively at sites of mislocalized, nascent NPCs, and NPC assembly completion is delayed. Our work implies that NPC spatial organization and number are independently regulated and suggests that torsinA is critical for the normal localization and assembly kinetics of NPCs.

References
1.
Kustedjo K, Bracey M, Cravatt B . Torsin A and its torsion dystonia-associated mutant forms are lumenal glycoproteins that exhibit distinct subcellular localizations. J Biol Chem. 2000; 275(36):27933-9. DOI: 10.1074/jbc.M910025199. View

2.
Ozelius L, Hewett J, Kramer P, Bressman S, Shalish C, De Leon D . Fine localization of the torsion dystonia gene (DYT1) on human chromosome 9q34: YAC map and linkage disequilibrium. Genome Res. 1997; 7(5):483-94. DOI: 10.1101/gr.7.5.483. View

3.
Vollmer B, Lorenz M, Moreno-Andres D, Bodenhofer M, De Magistris P, Astrinidis S . Nup153 Recruits the Nup107-160 Complex to the Inner Nuclear Membrane for Interphasic Nuclear Pore Complex Assembly. Dev Cell. 2015; 33(6):717-28. DOI: 10.1016/j.devcel.2015.04.027. View

4.
Soltysik K, Ohsaki Y, Tatematsu T, Cheng J, Maeda A, Morita S . Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner. J Cell Biol. 2020; 220(1). PMC: 7737703. DOI: 10.1083/jcb.202005026. View

5.
Tanabe L, Liang C, Dauer W . Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs. Cell Rep. 2016; 16(12):3322-3333. PMC: 5061049. DOI: 10.1016/j.celrep.2016.08.044. View