Journal Article (Review Article)

DZNE-2024-00438

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Proteomics elucidating physiological and pathological functions of TDP‐43

García Morato, J. (First author)DZNE* ; Gloeckner, C. J.DZNE* ; Kahle, P. (Last author)DZNE*

2023
Wiley VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/pmic.202200410

Abstract: 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.

Keyword(s): Proteomics (MeSH) ; Protein Aggregates (MeSH) ; DNA-Binding Proteins: genetics (MeSH) ; Ribonucleoproteins (MeSH)

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)
2. Functional Neuroproteomics and Translational Biomarkers in Neurodegenerative Diseases (AG Gloeckner)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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