Home > Publications Database > Proteomics elucidating physiological and pathological functions of TDP‐43 > print

001     269004
005     20240808173010.0
024 7 _ |a 10.1002/pmic.202200410
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037 _ _ |a DZNE-2024-00438
082 _ _ |a 540
100 1 _ |a García Morato, Jorge
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245 _ _ |a Proteomics elucidating physiological and pathological functions of TDP‐43
260 _ _ |a Weinheim
|c 2023
|b Wiley VCH
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520 _ _ |a 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.
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650 _ 2 |a Proteomics
|2 MeSH
650 _ 2 |a Protein Aggregates
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: genetics
|2 MeSH
650 _ 2 |a Ribonucleoproteins
|2 MeSH
700 1 _ |a Gloeckner, Christian Johannes
|0 P:(DE-2719)2811291
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700 1 _ |a Kahle, Philipp
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773 _ _ |a 10.1002/pmic.202200410
|g Vol. 23, no. 23-24, p. 2200410
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|t Proteomics
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856 4 _ |y OpenAccess
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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