About
Hebrew University of Jerusalem
Department of Cell and Developmental Biology
Cytoplasmic re-organization in response to stress conditions is essential for effective cellular stress response. Translational machinery is packaged into transient RNP granules, many biosynthetic enzymes are sequestered in storage granules, and misfolded proteins accumulate in dynamic inclusions with a diverse set of functions. All such compartments are not bound by membranes, and instead are thought to phase-separate into liquid-like droplets from free cytoplasm via low complexity hydrophobic promiscuous interactions. Under prolonged stress or energy depletion these droplets can progress towards insolubility and aggregation. This tendency of liquid-like cytoplasmic droplets to mature to solid phase structures translates into the pathological phenomenon of protein aggregation, and is highly relevant to understanding the onset of neurodegenerative diseases and the process of cellular aging. Our previous work suggests that this process is tightly regulated in the cell, but it is not clear how this regulation takes place.
In our current study, we set out to investigate the regulation of phase separation and aggregation in yeast, in response to stress. We used full genome screening and proteomic analysis to identify novel machinery regulating inclusion formation, processing, and spatiotemporal organization in the yeast cytoplasm. Surprisingly, we discovered a wide-spread involvement of endomembrane trafficking and biogenesis on inclusion biology and regulation of aggregation.