protein localization to phagophore assembly site

Definition

Target type: biologicalprocess

Any process in which a protein is transported to, or maintained at, the phagophore assembly site (PAS). [GOC:rb]

Protein localization to the phagophore assembly site is a crucial step in autophagy, a cellular process that degrades damaged or unwanted components. The phagophore, a double-membrane vesicle, originates from the endoplasmic reticulum (ER) and expands to engulf the cargo destined for degradation. This intricate process involves a complex interplay of proteins, each playing a specific role in ensuring the proper targeting and localization of proteins to the forming phagophore.

The journey of a protein to the phagophore assembly site starts with its recognition by autophagy receptors. These receptors, like p62/SQSTM1 and NBR1, bind to the cargo, which can be ubiquitinated proteins, aggregated proteins, or damaged organelles. Simultaneously, the receptors bind to the LC3 protein, a key component of the autophagosome membrane. This dual binding acts as a bridge, linking the cargo to the expanding phagophore.

The localization of LC3 to the phagophore assembly site is facilitated by its conjugation to phosphatidylethanolamine (PE) on the phagophore membrane. This process, termed LC3 lipidation, is mediated by a series of enzymes: ATG7, ATG3, and ATG12-ATG5-ATG16L1. The formation of the ATG12-ATG5-ATG16L1 complex acts as an E3-like ligase, facilitating the attachment of LC3 to PE. This lipidation event is crucial for the recruitment of LC3 to the phagophore and for the expansion of the phagophore membrane.

Additional proteins, like WIPI proteins and ATG14L, further contribute to the targeting and localization of proteins to the phagophore assembly site. WIPI proteins bind to phosphatidylinositol-3-phosphate (PI3P), a lipid that marks the phagophore membrane, and act as adaptors, facilitating the recruitment of other proteins to the assembly site. ATG14L, a component of the ULK1 kinase complex, is also implicated in the initiation and early steps of phagophore formation, further contributing to the precise localization of proteins to the site of autophagy.

The final step in the process involves the closure of the phagophore, forming a fully enclosed autophagosome. This autophagosome then fuses with lysosomes, where the cargo is degraded and recycled. The efficient and precise localization of proteins to the phagophore assembly site is crucial for the successful completion of autophagy, ensuring the removal of damaged or unwanted cellular components and maintaining cellular homeostasis.'
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Proteins (2)

Compounds (33)