Canuel Maryssa, Korkidakis Ann, Konnyu Kristin, Morales Carlos R
Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Strathcona Building, Room 1-1, Montreal, Que. H3A2BA, Canada.
Biochem Biophys Res Commun. 2008 Aug 22;373(2):292-7. doi: 10.1016/j.bbrc.2008.06.021. Epub 2008 Jun 16.
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.
可溶性溶酶体蛋白向溶酶体的转运主要依赖于甘露糖6-磷酸受体（M6PR）。然而，在I型细胞病（ICD）中，M6PR途径无功能，但一些可溶性溶酶体蛋白仍继续转运至溶酶体。在本文中，我们检验了组织蛋白酶D和H这两种表现出不依赖M6PR转运的可溶性蛋白酶通过sortilin靶向溶酶体的假说。使用显性负性sortilin构建体和小干扰RNA（siRNA），我们证明，虽然组织蛋白酶D转运部分依赖于sortilin，但组织蛋白酶H向溶酶体的转运完全依赖于sortilin。我们的结果表明，sortilin作为这些可溶性水解酶的M6PR替代分选受体发挥作用。
