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J. Cell Biol.,
Volume 140, Number 5, March 9, 1998 1075-1089
* Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500;
and Stable BHK cell lines inducibly expressing
wild-type or dominant negative mutant forms of the
rab7 GTPase were isolated and used to analyze the role
of a rab7-regulated pathway in lysosome biogenesis.
Expression of mutant rab7N125I protein induced a dramatic redistribution of cation-independent mannose
6-phosphate receptor (CI-MPR) from its normal perinuclear localization to large peripheral endosomes. Under these circumstances ~50% of the total receptor and
several lysosomal hydrolases cofractionated with light
membranes containing early endosome and Golgi
markers. Late endosomes and lysosomes were contained exclusively in well-separated, denser gradient
fractions. Newly synthesized CI-MPR and cathepsin D
were shown to traverse through an early endocytic
compartment, and functional rab7 was crucial for delivery to later compartments. This observation was evidenced by the fact that 2 h after synthesis, both markers
were more prevalent in fractions containing light membranes. In addition, both were sensitive to HRP-DAB-
mediated cross-linking of early endosomal proteins,
and the late endosomal processing of cathepsin D was
impaired. Using similar criteria, the lysosomal membrane glycoprotein 120 was not found accumulated in
an early endocytic compartment. The data are indicative of a post-Golgi divergence in the routes followed
by different lysosome-directed molecules.
Institut de Biolgie, Institut Pasteur de Lille, 59021 Lille, France
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