Measuring and Interpreting Nuclear Transport in Neurodegenerative Disease-The Example of C9orf72 ALS

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Sep 10

PMID 34502125

Citations 8

Authors

Marije F W Semmelink

Anton Steen

Liesbeth M Veenhoff

Affiliations

Soon will be listed here.

Abstract

Transport from and into the nucleus is essential to all eukaryotic life and occurs through the nuclear pore complex (NPC). There are a multitude of data supporting a role for nuclear transport in neurodegenerative diseases, but actual transport assays in disease models have provided diverse outcomes. In this review, we summarize how nuclear transport works, which transport assays are available, and what matters complicate the interpretation of their results. Taking a specific type of ALS caused by mutations in as an example, we illustrate these complications, and discuss how the current data do not firmly answer whether the kinetics of nucleocytoplasmic transport are altered. Answering this open question has far-reaching implications, because a positive answer would imply that widespread mislocalization of proteins occurs, far beyond the reported mislocalization of transport reporters, and specific proteins such as FUS, or TDP43, and thus presents a challenge for future research.

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