Mechanisms regulating the sorting of soluble lysosomal proteins

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Lysosomes are crucial organelles regulating cellular processes like metabolism, autophagy, and immune responses.
• Their function depends on specific membrane and soluble proteins, including hydrolases and activators for catabolism.
• Proper sorting of soluble lysosomal proteins is essential for lysosome function and cellular health.

Purpose of the Study:

• To review the mechanisms governing the sorting of soluble proteins to lysosomes.
• To highlight the impact of mutations in lysosomal protein sorting pathways on human diseases.
• To trace the journey of soluble lysosomal proteins from ER translation to trans-Golgi network sorting.

Main Methods:

• This review synthesizes existing literature on lysosomal protein sorting.
• It examines the molecular pathways involved in protein transport and localization.
• It correlates genetic mutations with observed human pathologies.

Main Results:

• Defects in soluble lysosomal protein sorting are linked to various human diseases.
• These include rare lysosome storage disorders and prevalent neurodegenerative conditions like Alzheimer's and Parkinson's disease.
• The review details the specific routes and molecular players involved in protein trafficking to lysosomes.

Conclusions:

• The precise sorting of soluble proteins to lysosomes is critical for cellular homeostasis.
• Mutations affecting this pathway have significant implications for human health, causing a spectrum of diseases.
• Understanding these mechanisms offers insights into disease pathogenesis and potential therapeutic targets.