Subcellular localization of mannose 6-phosphate glycoproteins in rat brain.
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 nonlysosomal 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.
Laboratory of Physiological Chemistry, Facultés Universitaires Notre-Dame de la Paix, B-5000 Namur, Belgium. michel.jadot@fundp.ac.be
M
M
Jadot
L
L
Lin
D E
DE
Sleat
I
I
Sohar
M S
MS
Hsu
J
J
Pintar
F
F
Dubois
S
S
Wattiaux-De Coninck
R
R
Wattiaux
P
P
Lobel
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008360:Mannosephosphates / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
D008360:Mannosephosphates; C027693:mannose-6-phosphate