TY  - JOUR
AU  - García Morato, Jorge
AU  - Gloeckner, Christian Johannes
AU  - Kahle, Philipp
TI  - Proteomics elucidating physiological and pathological functions of TDP‐43
JO  - Proteomics
VL  - 23
IS  - 23-24
SN  - 1615-9853
CY  - Weinheim
PB  - Wiley VCH
M1  - DZNE-2024-00438
SP  - 2200410
PY  - 2023
AB  - 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.
KW  - Proteomics
KW  - Protein Aggregates
KW  - DNA-Binding Proteins: genetics
KW  - Ribonucleoproteins
LB  - PUB:(DE-HGF)16
C6  - pmid:37671599
DO  - DOI:10.1002/pmic.202200410
UR  - https://pub.dzne.de/record/269004
ER  -