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First published online 14 November 2006
doi: 10.1242/jcs.03283

Journal of Cell Science 119, 4935-4943 (2006)
Published by The Company of Biologists 2006
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Research Article

The 46-kDa mannose 6-phosphate receptor does not depend on endosomal acidification for delivery of hydrolases to lysosomes

Olivia C. Probst1, Phuong Ton2, Barbara Svoboda1, Andrew Gannon2, Werner Schuhmann1, Johannes Wieser1, Regina Pohlmann3 and Lukas Mach1,2,*

1 Institut für Angewandte Genetik und Zellbiologie, Universität für Bodenkultur Wien, Muthgasse 18, 1190 Vienna, Austria
2 Department of Biochemistry, University of Western Australia, Nedlands, WA 6907, Australia
3 Institut für Physiologische Chemie und Pathobiochemie, Universität Münster, Waldeyerstr. 15, 48149 Münster, Germany

* Author for correspondence (e-mail: lukas.mach{at}boku.ac.at)

Accepted 28 September 2006

In mammalian cells, the mannose 6-phosphate receptor pathway accounts for the transport of most soluble acid hydrolases to lysosomes. It is believed that dissociation of mannose 6-phosphate receptors and their ligands is entirely driven by the acidic environment in endosomal compartments. Indeed, pH-perturbing substances such as ammonium chloride and monensin have been shown to inhibit lysosomal enzyme targeting in cells that express both known mannose 6-phosphate receptors. We now demonstrate that ammonium chloride and monensin exert modest effects on the intracellular retention of lysosomal hydrolases in murine cells that synthesize only the 46-kDa mannose 6-phosphate receptor. Neither ammonium chloride nor monensin induces changes to the subcellular localization of lysosomal hydrolases and the 46-kDa mannose 6-phosphate receptor in these cells. This suggests that endosomal dissociation of the receptor and its ligands still occurs in the presence of these agents. We conclude that the murine 46-kDa mannose 6-phosphate receptor has the capacity to deliver its cargo proteins to lysosomes even in the absence of endosomal acidification.

Key words: Mannose 6-phosphate, Lysosome, Trafficking, Cathepsin, Hydrolase, Biosynthesis


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