Post-Translational Modifications Modulate Proteinopathies of TDP-43, FUS and hnRNP-A/B in Amyotrophic Lateral Sclerosis
抄録
<jats:p>It has been shown that protein low-sequence complexity domains (LCDs) induce liquid-liquid phase separation (LLPS), which is responsible for the formation of membrane-less organelles including P-granules, stress granules and Cajal bodies. Proteins harbouring LCDs are widely represented among RNA binding proteins often mutated in ALS. Indeed, LCDs predispose proteins to a prion-like behaviour due to their tendency to form amyloid-like structures typical of proteinopathies. Protein post-translational modifications (PTMs) can influence phase transition through two main events: i) destabilizing or augmenting multivalent interactions between phase-separating macromolecules; ii) recruiting or excluding other proteins and/or nucleic acids into/from the condensate. In this manuscript we summarize the existing evidence describing how PTM can modulate LLPS thus favouring or counteracting proteinopathies at the base of neurodegeneration in ALS.</jats:p>
収録刊行物
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- Frontiers in Molecular Biosciences
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Frontiers in Molecular Biosciences 8 585-, 2021-07-05
Frontiers Media SA