complexesESCRT0

ESCRT-0 is a protein complex involved in the endosomal sorting pathway. It plays a crucial role in the cell's ability to process and degrade internalized material. The complex is primarily responsible for recognizing and binding to ubiquitinated proteins that are destined for degradation in the lysosome. It acts as an initial recognition module within the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery.

The ESCRT-0 complex is composed of two core proteins, Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) and Alix (also known as ALG-2-interacting protein X). Hrs is a key component that contains multiple domains, including a ubiquitin-interacting motif (UIM) and a phosphatidylinositol-3-phosphate (PI3P)-binding FYVE domain. These domains allow Hrs to bind to ubiquitinated cargo and to the endosomal membrane. Alix, while not always considered a core component of ESCRT-0 itself, interacts with Hrs and other ESCRT proteins, contributing to the assembly and function of the complex.

The primary function of ESCRT-0 is to initiate the sorting of ubiquitinated transmembrane proteins away from the limiting membrane of the endosome and into intraluminal vesicles (ILVs). This process is essential for various cellular functions, including receptor downregulation, pathogen sequestration, and the formation of multivesicular bodies (MVBs). Without functional ESCRT-0, cells can exhibit defects in MVB formation and impaired protein degradation, potentially leading to cellular dysfunction and disease. ESCRT-0 acts as a scaffold, recruiting subsequent ESCRT complexes (ESCRT-I, -II, and -III) to further facilitate cargo sorting and membrane budding.