| Description |
The ESCRT (endosomal sorting complexes required for transport) protein complexes are required for the sorting of proteins into the MVB (multivesicular body) pathway, a protein trafficking pathway that is critical for the degradation of plasma membrane proteins. As a result, the ESCRTs plays an important role in the regulation of nutrient import and cell signaling events by influencing the expression of nutrient transporters and signaling receptors on the surface of the cell. In this study we present a novel in vitro technique based on SFG (sumfrequency generation) capable of analyzing the dynamic assembly of the ESCRT complexes on planar supported lipid bilayers. We present evidence to support that this novel approach has the potential to provide information about the dynamics of the ESCRT network and to obtain data regarding the function of these protein complexes. Furthermore, we elucidated a regulatory connection between the nutrient sensing system, TORC1 (target of rapamycin complex 1), and the MVB pathway. Our results demonstrate that the MVB pathway functions to degrade non-essential biomass during starvation to replenish depleted amino acid levels. We further propose that ESCRT-dependent protein turnover is regulated by the metabolic state of the cell through TORC1 signaling. Surprisingly, we found indications that endocytosis and subsequent degradation of plasma membrane proteins is regulated by a novel starvation pathway that acts independently of TORC1. Based on our results, we present a model in which during starvation TORC1, together with an unknown regulatory pathway, increases the sorting efficiency and degradation of cargo proteins through the MVB pathway by suppressing recycling pathways. The increase in protein turnover replenishes the free amino acid pool, which allows the cell to produce stress-response proteins required to adapt to starvation conditions. |
