%0 Journal Article
%A García Morato, Jorge
%A Gloeckner, Christian Johannes
%A Kahle, Philipp
%T Proteomics elucidating physiological and pathological functions of TDP‐43
%J Proteomics
%V 23
%N 23-24
%@ 1615-9853
%C Weinheim
%I Wiley VCH
%M DZNE-2024-00438
%P 2200410
%D 2023
%X Trans-activation response DNA binding protein of 43 kDa (TDP-43) regulates a great variety of cellular processes in the nucleus and cytosol. In addition, a defined subset of neurodegenerative diseases is characterized by nuclear depletion of TDP-43 as well as cytosolic mislocalization and aggregation. To perform its diverse functions TDP-43 can associate with different ribonucleoprotein complexes. Combined with transcriptomics, MS interactome studies have unveiled associations between TDP-43 and the spliceosome machinery, polysomes and RNA granules. Moreover, the highly dynamic, low-valency interactions regulated by its low-complexity domain calls for innovative proximity labeling methodologies. In addition to protein partners, the analysis of post-translational modifications showed that they may play a role in the nucleocytoplasmic shuttling, RNA binding, liquid-liquid phase separation and protein aggregation of TDP-43. Here we review the various TDP-43 ribonucleoprotein complexes characterized so far, how they contribute to the diverse functions of TDP-43, and roles of post-translational modifications. Further understanding of the fluid dynamic properties of TDP-43 in ribonucleoprotein complexes, RNA granules, and self-assemblies will advance the understanding of RNA processing in cells and perhaps help to develop novel therapeutic approaches for TDPopathies.
%K Proteomics
%K Protein Aggregates
%K DNA-Binding Proteins: genetics
%K Ribonucleoproteins
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37671599
%R 10.1002/pmic.202200410
%U https://pub.dzne.de/record/269004