Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Inhibition of calcium-independent mannose 6-phosphate receptor incorporation into trans-Golgi network-derived clathrin-coated vesicles by wortmannin

Gaffet, P., Jones, Arwyn Tomos and Clague, M. J. 1997. Inhibition of calcium-independent mannose 6-phosphate receptor incorporation into trans-Golgi network-derived clathrin-coated vesicles by wortmannin. Journal of Biological Chemistry 272 (39) , pp. 24170-24175. 10.1074/jbc.272.39.24170

Full text not available from this repository.

Abstract

The transport of pro-cathepsin D from thetrans-Golgi network (TGN) to the endosomal pathway is dependent on binding to the calcium-independent mannose 6-phosphate receptor (ci-M6PR), which is incorporated into TGN-derived clathrin-coated transport vesicles (CCVs). Inhibition of this transport step by wortmannin has led to the proposal that it is dependent upon a phosphoinositide 3-kinase activity necessary for ci-M6PR recruitment into TGN-derived CCVs or in the formation of those vesicles (Brown, W. J., DeWald, D. B., Emr, S. D., Plutner, H., and Balch, W. E. (1995) J. Cell Biol. 130, 781–796; Davidson, H. W. (1995) J. Cell Biol. 130, 797–806). In this study we have addressed the effect of wortmannin on the TGN step of the ci-M6PR cycle. CCVs from K562 cells, pretreated or not with 250 nm wortmannin, were purified on equilibrium density gradients. Quantification of TGN-derived CCVs, assessed by γ-adaptin content in purified vesicle fractions, showed that the formation of the vesicles was only marginally decreased after 20 min of treatment with the drug, while for the same wortmannin treatment, the amount of ci-M6PR recruited into those vesicles was decreased by 70% compared with control. At a later time point (2 h), a reduction in the amount of γ-adaptin in CCV fractions was also observed. These findings demonstrate that inhibition of ci-M6PR recruitment into CCVs but not of vesicle formation is the primary reason for the observed defect in cathepsin D transport following wortmannin treatment.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 0021-9258
Last Modified: 04 Jun 2017 07:45
URI: http://orca-mwe.cf.ac.uk/id/eprint/67571

Citation Data

Cited 29 times in Google Scholar. View in Google Scholar

Cited 29 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item