Nuclear-Import Receptors Counter Deleterious Phase Transitions in Neurodegenerative Disease.

ABSTRACT: Nuclear-import receptors (NIRs) engage nuclear-localization signals (NLSs) of polypeptides in the cytoplasm and transport these cargo across the size-selective barrier of the nuclear-pore complex into the nucleoplasm. Beyond this canonical role in nuclear transport, NIRs operate in the cytoplasm to chaperone and disaggregate NLS-bearing clients. Indeed, NIRs can inhibit and reverse functional and deleterious phase transitions of their cargo, including several prominent neurodegenerative disease-linked RNA-binding proteins (RBPs) with prion-like domains (PrLDs), such as TDP-43, FUS, EWSR1, TAF15, hnRNPA1, and hnRNPA2. Importantly, elevated NIR expression can mitigate degenerative phenotypes connected to aberrant cytoplasmic aggregation of RBPs with PrLDs. Here, we review recent discoveries

SUBMITTER: Odeh HM 

PROVIDER: S-EPMC8748273 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature