Targeting of non-phosphorylated lysosomal enzymes involves secretion and Lrp1-mediated recapture

Most lysosomal enzymes require mannose 6-phosphate (M6P) residues for efficient receptor-mediated lysosomal targeting. Although the lack of M6P results in missorting and hypersecretion, selected lysosomal enzymes reach normal levels in lysosomes of various cell types suggesting the existence of M6P-independent transport routes. SILAC-based analysis of purified lysosomes from M6P-deficient mouse fibroblasts (PTki) revealed unchanged amounts of 11 lysosomal enzymes, including cathepsin D and B (CtsD, CtsB), while demonstrating mossiorting of a variety of soluble lysosomal enzymes