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Optimized Protocol for the Extraction of Proteins from the Human Mitral Valve

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Prosaposin: a protein with differential sorting and multiple functions.

L Carvelli¹, Y Libin¹, C R Morales²

¹Department of Anatomy and Cell Biology, McGill University.

Histology and Histopathology

|December 19, 2014

Summary

This summary is machine-generated.

A novel lysosomal sorting receptor, sortilin, was discovered through studying prosaposin trafficking. Sortilin binds prosaposin

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Published on: March 9, 2010

Area of Science:

Cell Biology
Molecular Biology
Neuroscience

Background:

Protein trafficking in eukaryotes relies on the endoplasmic reticulum and Golgi apparatus for modification, sorting, and distribution.
Lysosomal proteins are typically directed via mannose-6-phosphate receptors (MPR), but exceptions exist.
I-cell disease revealed an MPR-independent pathway for lysosomal targeting.

Purpose of the Study:

To elucidate the mechanism of lysosomal targeting for prosaposin, particularly in the context of MPR pathway disruptions.
To identify the specific protein interactions and motifs responsible for prosaposin's lysosomal localization.
To explore the broader functions and distribution of prosaposin beyond its lysosomal role.

Main Methods:

Investigated prosaposin trafficking in relation to lysosomal sorting pathways.
Utilized deletion and mutational analysis of prosaposin's C-terminus.
Examined the interaction between prosaposin and its newly identified receptor, sortilin.
Assessed the extracellular functions of prosaposin in nervous tissues.

Main Results:

Discovery of sortilin as a novel lysosomal sorting receptor for prosaposin.
Identified the C-terminus of prosaposin, specifically a motif in its first half, as crucial for sortilin binding and lysosomal transport.
Demonstrated that prosaposin can be secreted extracellularly, influencing nervous system functions.
Confirmed prosaposin's presence in various bodily fluids, suggesting diverse physiological roles.

Conclusions:

Sortilin mediates lysosomal targeting of prosaposin through C-terminal interactions, independent of the MPR pathway.
Prosaposin exhibits extracellular functions impacting nervous system signaling.
Prosaposin is a multifunctional protein with roles beyond lysosomal homeostasis, essential for nervous system development and maintenance.