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IRB Research Node/IBEC Joint Seminar: Nunilo Cremades
Thursday, January 19, 2023 @ 9:30 am–11:30 am
Date: Thursday 19 January 2023, 9:30h
Place: Felix Serratosa Hall, PCB
Speaker: Nunilo Cremades, PhD – Associate Professor at Dept. Biochemistry and Molecular and Cellular Biology and Group Leader at Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, Spain
Title: Liquid-liquid phase separation and co-aggregation of neurodegenerative disease-related alpha-synuclein and Tau proteins
Host: Xavier Salvatella (IRB) & Benedetta Bolognesi (IBEC)
Abstract:
Spatial segregation in the cell can be achieved through the formation of protein-rich liquid-like dense bodies, termed biomolecular condensates or liquid droplets, through a process known as liquid-liquid phase separation (LLPS). Emerging evidence supports the hypothesis that aberrant protein-driven LLPS and the transition of the liquid droplets to solid-like structures might be a relevant cellular pathway leading to the formation of amyloid, toxic aggregates that are often a hallmark of relevant neurodegenerative diseases. A number of experimental studies have highlighted the flexible, typically disordered and ‘multivalent’ nature of the constituent proteins in these liquid-like condensates, although less is known about the particular molecular determinants governing the growth and maturation of these condensates into more solid-like states. While the LLPS process of Tau, the protein that is generally associated with Alzheimer´s disease, has been recently clarified, that of alpha-synuclein (αS), the protein linked to Parkinson´s disease, remains obscure. In this talk, I will show our recent findings that demonstrate that αS actively phase-separates into liquid condensates by electrostatic complex coacervation with positively charged polypeptides such as Tau. By combining a set of advanced biophysical techniques, we have been able to characterize αS/Tau LLPS and identified key factors leading to the co-aggregation of both proteins inside the coacervates. The mechanism of co-aggregation between αS and Tau that we have identified could be the basis for the in vivo formation of αS/Tau hetero-aggregates observed in the brains of patients suffering from synucleinopathies.
