protein targeting to lysosome

Definition

Target type: biologicalprocess

The process of directing proteins towards the lysosome using signals contained within the protein. [GOC:curators]

Protein targeting to lysosomes is a complex and highly regulated process essential for maintaining cellular homeostasis. It involves the delivery of proteins, including soluble enzymes, transmembrane proteins, and receptors, from the trans-Golgi network (TGN) to the lysosome, where they are degraded or sorted for other cellular destinations. The process relies on a series of molecular signals embedded within the target proteins and the intricate machinery of the secretory pathway.

The journey begins with the synthesis of proteins destined for the lysosome on ribosomes attached to the endoplasmic reticulum (ER). These proteins typically possess a unique sorting signal known as a lysosomal targeting signal (LTS), which directs them to the lysosomal pathway. Several types of LTS have been identified, including:

1. **Mannose-6-phosphate (M6P) residues:** The most common and well-characterized LTS. M6P residues are added to lysosomal hydrolases in the Golgi apparatus, specifically in the cis-Golgi, through a series of enzymatic reactions. These residues are recognized by M6P receptors present on the TGN membrane.

2. **Other signals:** While M6P-mediated sorting is the dominant mechanism, other signals, including dileucine motifs, tyrosine-based signals, and GPI anchors, have also been identified and contribute to lysosomal targeting.

Once the proteins reach the TGN, they interact with the M6P receptors, initiating their journey to the lysosome. The M6P receptor-ligand complex moves through the TGN and is packaged into clathrin-coated vesicles. These vesicles bud off from the TGN and fuse with late endosomes, acidic compartments that serve as intermediates in the lysosomal pathway.

Inside the late endosomes, the acidic environment triggers the dissociation of the M6P receptor from the lysosomal hydrolases. The receptors cycle back to the TGN for further rounds of cargo transport, while the lysosomal enzymes are retained within the late endosomes.

Finally, the late endosomes mature into lysosomes, acidic organelles containing a diverse array of hydrolytic enzymes capable of degrading various cellular components, including proteins, lipids, and carbohydrates.

This intricate targeting process ensures the efficient delivery of lysosomal enzymes to their designated destination, enabling the lysosome to perform its critical role in cellular recycling and degradation. Defects in this pathway can lead to various lysosomal storage disorders, highlighting the importance of precise protein sorting for maintaining cellular homeostasis and preventing disease.'
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Proteins (6)

Compounds (33)