Protein Phase Separation and Aggregation in (Patho)Physiology of Neurons

Liquid-liquid phase separation (LLPS) is emerging as a major mechanism for the organization of macromolecules in compartments non-limited by a membrane or scaffold. In the last several years, a surge of studies shows that spatial and temporal organization of many structures in neurons is formed via LLPS, such as SV clusters, stress granules, active zones, post-synaptic densities (both excitatory and inhibitory). The lack of regulation of LLPS in neurons leads to protein and organelle aggregation, which are the hallmark of many neurodegenerative diseases.

In this Research Topic, we want to achieve three aspects. First, to introduce how LLPS principles help us understand the mesoscale organization of neurons. Second, to discuss the limitations of the current techniques in scrutinizing the concept of LLPS in vitro, emphasizing the need for developing new approaches. Third, to address the functional implications of LLPS for membrane trafficking and synaptic function both in physiology and disease.

We are looking for both original research and review articles covering:
(i) emerging roles of LLPS in neurobiology;
(ii) development of novel techniques to characterize LLPS in living systems;
(iii) regulation of protein phase separation versus aggregation
(iv) roles for LLPS of neuronal proteins implicated in neurodegenerative diseases (e.g., alpha-synuclein, FUS, TDP43).