protein targeting to lysosome involved in chaperone-mediated autophagy

Definition

Target type: biologicalprocess

The targeting of a protein to the lysosome process in which an input protein binds to a chaperone and subsequently to a lysosomal receptor. [GOC:dph, GOC:pad, GOC:PARL, PMID:22748206]

Chaperone-mediated autophagy (CMA) is a selective pathway for the lysosomal degradation of specific proteins. This process involves the recognition of target proteins by chaperones, their delivery to the lysosome, and their subsequent degradation.

1. **Target Recognition:** CMA begins with the recognition of specific target proteins by the chaperone protein **heat shock cognate 70 (HSC70)**. These target proteins often contain a specific amino acid sequence known as a **KFERQ-like motif**, which serves as a signal for CMA.

2. **Chaperone Binding:** HSC70 binds to the KFERQ-like motif in the target protein, facilitating its unfolding and preventing aggregation.

3. **Delivery to the Lysosome:** The HSC70-bound target protein is then transported to the lysosome, where it interacts with the lysosomal membrane protein **LAMP-2A**.

4. **Lysosomal Translocation:** LAMP-2A acts as a receptor for the target protein. The complex of HSC70, target protein, and LAMP-2A translocates across the lysosomal membrane via a complex process that involves unfolding the target protein and threading it through a pore in the membrane.

5. **Degradation:** Once inside the lysosome, the target protein is degraded by lysosomal enzymes.

CMA is a highly regulated process that is essential for maintaining cellular homeostasis. It plays a role in the degradation of damaged or misfolded proteins, the removal of long-lived proteins, and the regulation of cellular signaling pathways. Dysregulation of CMA has been implicated in various diseases, including neurodegenerative disorders, cancer, and aging.'
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Proteins (2)

Compounds (9)