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Published on: January 11, 2017
Sortilin and prosaposin localize to detergent-resistant membrane microdomains
Maryssa Canuel1, Nihar Bhattacharyya, Alejandro Balbis
1Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montreal, Quebec, Canada, H3A 2B2.
Experimental Cell Research
|November 11, 2008
Summary
Sortilin and the mannose 6-phosphate receptor (M6PR) localize to detergent-resistant membranes (DRMs), facilitating lysosomal protein sorting. Prosaposin requires sortilin to be recruited to these specialized membrane platforms for lysosomal delivery.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Lysosomal proteins are primarily sorted via the mannose 6-phosphate receptor (M6PR) in the trans-Golgi network.
- Sortilin mediates the lysosomal trafficking of prosaposin and certain hydrolases.
- Prosaposin's lysosomal targeting is known to depend on sphingomyelin.
Purpose of the Study:
- To investigate the hypothesis that sortilin and its ligands reside in detergent-resistant membranes (DRMs).
- To determine if M6PR and its cargo also localize to DRMs.
- To elucidate the role of sortilin in prosaposin recruitment to DRMs.
Main Methods:
- Analysis of detergent-resistant membrane (DRM) fractions.
- Detection of sortilin, prosaposin, M6PR, cathepsin B, cathepsin H, and cathepsin D in DRM fractions.
- Utilized sortilin shRNA to assess prosaposin localization.
Main Results:
- Sortilin and its ligand, prosaposin, were detected in DRM fractions.
- The M6PR and its cargo, cathepsin B, were also found in DRMs.
- Cathepsin H and cathepsin D, interacting with sortilin and/or M6PR, were present in DRMs.
- Prosaposin's localization to DRMs was dependent on the presence of sortilin.
Conclusions:
- Both sortilin and M6PR localize to similar membrane platforms (DRMs).
- Prosaposin requires interaction with sortilin for recruitment to DRMs.
- This suggests a shared mechanism involving membrane platforms for the trafficking of different lysosomal proteins.
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