Quality control in the endoplasmic reticulum: PDI mediates the ER retention of unassembled procollagen C-propeptides

Bottomley, M.J., Batten, M.R., Lumb, R.A. and Bulleid, N.J. (2001) Quality control in the endoplasmic reticulum: PDI mediates the ER retention of unassembled procollagen C-propeptides. Current Biology, 11(14), pp. 1114-1118. (doi:10.1016/S0960-9822(01)00317-7)

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Quality control within the endoplasmic reticulum (ER) is thought to be mediated by the interaction of a folding protein with one or several resident ER proteins [1]. Protein disulphide isomerase (PDI) is one such ER resident protein that has been previously shown to interact with proteins during their folding and assembly pathways [2] and [3]. It has been assumed that, as a consequence of this interaction, unassembled proteins are retained within the ER. Here, we experimentally show that this is indeed the case. We have taken advantage of our previous finding that PDI interacts with procollagen chains early on in their assembly pathway [2] to address the role of this protein in directly retaining unassembled chains within the ER. Our experimental approach involved expressing individual C-propeptide domains from different procollagen chains in mammalian cells and determining the ability of these domains to interact with PDI and to be secreted. The C-propeptide from the proα2(I) chain was retained within the cell, where it formed a complex with PDI. Conversely, the C-propeptide from the proα1(III) chain did not form a complex with PDI and was secreted. Both domains were secreted, however, from a stable cell line expressing a secreted form of PDI lacking its ER retrieval signal. Hence, we have demonstrated directly that the intracellular retention of one substrate for ER quality control is due to an interaction with PDI.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Bulleid, Professor Neil
Authors: Bottomley, M.J., Batten, M.R., Lumb, R.A., and Bulleid, N.J.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Current Biology
Published Online:15 August 2001

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