The Library
Ferroportin : lack of evidence for multimers
Tools
Schimanski, Lisa M., Drakesmith, Hal, Talbott, Charlotte, Horne, Kerry, James, John R., Davis, Simon J., Sweetland, Emma, Bastin, Judy, Cowley, Diana and Townsend, Alain R.M. (2008) Ferroportin : lack of evidence for multimers. Blood Cells, Molecules, and Diseases, 40 (3). pp. 360-369. doi:10.1016/j.bcmd.2007.09.007 ISSN 10799796.
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.1016/j.bcmd.2007.09.007
Abstract
Ferroportin is a multi-transmembrane glycoprotein that mediates iron export from cells. Mutations in ferroportin are linked to type IV hemochromatosis, a dominantly inherited disorder of iron metabolism. Multimers of ferroportin, whose existence may relate to the dominant inheritance pattern of disease, have been detected in some studies but not others. We looked for evidence of multimerization in several different types of experiment. We assayed the maturation of mutant and wild-type ferroportin and found that loss-of-function mutants had a reduced half-life but did not alter the stability of coexpressed wild-type. Using bioluminescence resonance energy transfer analysis, we tested how mature wild-type ferroportin behaved in intact live cell membranes. Ferroportin–ferroportin interactions gave the very low acceptor/donor ratio-independent energy transfer levels characteristic of random protein–protein interactions, consistent with ferroportin behaving as a monomer. Consistent with these experiments, we were unable to detect a dominant negative functional effect of mutant ferroportin on wild-type, even when expression of wild-type protein was titrated to low levels. These data suggest that dominantly inherited ferroportin disease does not result from the direct action of a mutated protein inhibiting a wild-type protein within multimers. We propose other possible mechanisms of disease.
Item Type: | Journal Article | ||||||
---|---|---|---|---|---|---|---|
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||||
Journal or Publication Title: | Blood Cells, Molecules, and Diseases | ||||||
Publisher: | Elsevier | ||||||
ISSN: | 10799796 | ||||||
Official Date: | May 2008 | ||||||
Dates: |
|
||||||
Volume: | 40 | ||||||
Number: | 3 | ||||||
Page Range: | pp. 360-369 | ||||||
DOI: | 10.1016/j.bcmd.2007.09.007 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |