Granulins modulate liquid–liquid phase separation and aggregation of the prion-like C-terminal domain of the neurodegeneration-associated protein TDP-43
Anukool A. Bhopatkar, Vladimir N. Uversky, Vijayaraghavan Rangachari
Abstract
GRN-3 promoted insoluble aggregates of the TDP-43 CTD while GRN-5 mediated liquid-liquid phase separation. These results constitute the first observation of an interaction between GRNs and TDP-43, suggesting a mechanism by which attenuated PGRN function could lead to familial FTLD or ALS.
Topics & Concepts
NeurodegenerationTerminal (telecommunication)Prion proteinChemistryProtein aggregationBiophysicsDomain (mathematical analysis)Liquid phasePhase (matter)Cell biologyBiochemistryBiologyComputer sciencePhysicsOrganic chemistryPathologyMathematical analysisMathematicsThermodynamicsTelecommunicationsDiseaseMedicineAmyotrophic Lateral Sclerosis ResearchRNA Research and SplicingHereditary Neurological Disorders