Sortilin mediates the lysosomal targeting of cathepsins D and H
M Canuel, A Korkidakis, K Konnyu… - … and biophysical research …, 2008 - Elsevier
M Canuel, A Korkidakis, K Konnyu, CR Morales
Biochemical and biophysical research communications, 2008•ElsevierDelivery 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 …
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 …
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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