Subcellular localization of mannose 6-phosphate glycoproteins in rat brain

Michel Jadot, Li Lin, David E. Sleat, Istvan Sohar, Ming Sing Hsu, John Pintar, Franz Dubois, Simone Wattiaux-de Coninck, Robert Wattiaux, Peter Lobel

Research output: Contribution to journalArticlepeer-review


The intracellular transport of soluble lysosomal enzymes relies on the post-translational modification of N-linked oligosaccharides to generate mannose 6-phosphate (Man 6-P) residues. In most cell types the Man 6-P signal is rapidly removed after targeting of the precursor proteins from the Golgi to lysosomes via interactions with Man 6-phosphate receptors. However, in brain, the steady state proportion of lysosomal enzymes containing Man 6-P is considerably higher than in other tissues. As a first step toward understanding the mechanism and biological significance of this observation, we analyzed the subcellular localization of the rat brain Man 6-P glycoproteins by combining biochemical and morphological approaches. The brain Man 6-P glycoproteins are predominantly localized in neuronal lysosomes with no evidence for a steady state localization in nonlysosoreal or prelysosomal compartments. This contrasts with the clear endosome-like localization of the low steady state proportion of mannose-6-phosphorylated lysosomal enzymes in liver. It therefore seems likely that the observed high percentage of phosphorylated species in brain is a consequence of the accumulation of lysosomal enzymes in a neuronal lysosome that does not fully dephosphorylate the Man 6-P moieties.

Original languageEnglish
Pages (from-to)21104-21113
Number of pages10
JournalJournal of Biological Chemistry
Issue number30
Publication statusPublished - 23 Jul 1999


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