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Aerts, J.M.F.G.

Geuze, H.J.

Kal, A.J.

Rijnboutt, S.

Strous, G.J.

We have studied the role of N-linked oligosaccharides and proteolytic processing on the targeting of cathepsin D to the lysosomes in the human hepatoma cell line HepG2. In the presence of tunicamycin cathepsin D was synthesized as an unglycosylated 43-kDa proenzyme which was proteolytically processed via a 39-kDa intermediate to a 28-kDa mature form. Only a small portion was secreted into the culture medium. During intracellular transport the 43-kDa procathepsin D transiently became membrane-associated independently of binding to the mannose 6-phosphate receptor. Subcellular fractionation showed that unglycosylated cathepsin D was efficiently targeted to the lysosomes via intermediate compartments similar to the enzyme in control cells. The results show that in HepG2 cells processing and transport of cathepsin D to the lysosomes is independent of mannose 6-phosphate residues. Inhibition of the proteolytic processing of 53-kDa procathepsin D by protease inhibitors caused this form to accumulate intracellularly. Subcellular fractionation revealed that the procathepsin D was transported to lysosomes, thereby losing its membrane association. Procathepsin D taken up by the mannose 6-phosphate receptor also transiently became membrane-associated, probably in the same compartment. We conclude that the mannose 6-phosphate-independent membrane-association is a transient and compartment-specific event in the transport of procathepsin 

Kal, A. J.

Geuze, H. J.

Aerts, H.

Strous, G. J.

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Mannose 6-phosphate-independent targeting of cathepsin D to lysosomes in HepG2 cells

Leiden University Scholary Publications

Mannose 6-phosphate independent targeting of cathepsin D to lysosomes in HepG2 cells

https://scholarlypublications.universiteitleiden.nl/access/item%3A2865348/download

Mannose 6-phosphate independent targeting of cathepsin D to lysosomes in HepG2 cells

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Leiden University Scholary Publications

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