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Updated: Jul 4, 2026

Detection of Detergent-sensitive Interactions Between Membrane Proteins
Published on: March 7, 2018
Sortilin mediates the lysosomal targeting of cathepsins D and H
Maryssa Canuel1, Ann Korkidakis, Kristin Konnyu
1Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Strathcona Building, Room 1-1, Montreal, Que. H3A2BA, Canada.
Abstract:
Delivery of soluble lysosomal proteins to the lysosomes is dependent primarily on the mannose 6-phosphate receptor (M6PR). However, in I-cell disease (ICD), in which the M6PR pathway is non-functional, some soluble lysosomal proteins continue to traffic to the lysosomes. In this paper, we tested the hypothesis that cathepsins D and H, two soluble proteases that exhibit M6PR-independent trafficking, are targeted to the lysosomes by sortilin. Using a dominant-negative sortilin construct and small interfering RNA (siRNA) we demonstrated that while cathepsin D transport is partially dependent upon sortilin, cathepsin H requires exclusively sortilin for its transport to the lysosomes. Our results suggest that sortilin functions as an alternative sorting receptor to the M6PR for these soluble hydrolases.
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