Mutants of neuroserpin that cause dementia accumulate as polymers within the endoplasmic reticulum.

The Journal of Biological Chemistry
Elena MirandaDavid A Lomas

Abstract

The dementia familial encephalopathy with neuroserpin inclusion bodies (FENIB) is caused by the accumulation of mutant neuroserpin within neurons (Davis, R. L., Shrimpton, A. E., Holohan, P. D., Bradshaw, C., Feiglin, D., Sonderegger, P., Kinter, J., Becker, L. M., Lacbawan, F., Krasnewich, D., Muenke, M., Lawrence, D. A., Yerby, M. S., Shaw, C.-M., Gooptu, B., Elliott, P. R., Finch, J. T., Carrell, R. W., and Lomas, D. A. (1999) Nature 401, 376-379), but little is known about the trafficking of wild type and mutant neuroserpins. We have established a cell model to study the processing of wild type neuroserpin and the Syracuse (S49P) and Portland (S52R) mutants that cause FENIB. Here we show that Syracuse and Portland neuroserpin are retained soon after their synthesis in the endoplasmic reticulum and that the limiting step in their processing is the transport to the Golgi complex. This is in contrast to the wild type protein, which is secreted into the culture medium. Mutant neuroserpin is retained within the endoplasmic reticulum as polymers, similar to those isolated from the intraneuronal inclusions in the brains of individuals with FENIB. Remarkably, the Portland mutant showed faster accumulation and slower secretion compa...Continue Reading

References

Apr 1, 1989·The Journal of Clinical Investigation·J A CarlsonS L Woo
Jan 1, 1983·Methods in Enzymology·P O Seglen
Aug 1, 1996·Nature Structural Biology·P R ElliottJ P Abrahams
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·E D WernerA A McCracken
Jul 12, 1997·Lancet·R W Carrell, D A Lomas
Mar 27, 1999·The Journal of Biological Chemistry·T R DaffornD A Lomas
Apr 9, 1999·The Journal of Clinical Investigation·R MahadevaD A Lomas
Dec 14, 1999·The American Journal of Pathology·R L DavisD A Lawrence
Aug 5, 2000·The Journal of Biological Chemistry·P SivasothyD A Lomas
Oct 29, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·J H Teckman, D H Perlmutter
Dec 21, 2000·Trends in Cell Biology·R R Kopito
Jan 6, 2001·The American Journal of Pathology·M YazakiM D Benson
Jan 5, 2002·The New England Journal of Medicine·Robin W Carrell, David A Lomas
Apr 30, 2002·Human Molecular Genetics·Brinda RavikumarDavid C Rubinsztein
Sep 14, 2002·The Journal of Biological Chemistry·Karen Barker-CarlsonBradford S Schwartz
Oct 2, 2002·Journal of Neurochemistry·Parmjeet K ParmarNigel P Birch
Oct 3, 2002·Nature Reviews. Genetics·David A Lomas, Robin W Carrell
Oct 26, 2002·The Journal of Biological Chemistry·Yuki TanakaTsuneo Imanaka
Nov 20, 2002·Annals of the New York Academy of Sciences·Rena M HillNigel P Birch
Jun 17, 2003·The Journal of Biological Chemistry·Helen ParfreyDavid A Lomas
Jun 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ying WuRichard N Sifers

❮ Previous
Next ❯

Citations

Jan 15, 2008·Journal of Inherited Metabolic Disease·C M GreeneN G McElvaney
Jul 2, 2008·The Journal of Experimental Medicine·Bibek Gooptu, David A Lomas
Mar 23, 2011·Cold Spring Harbor Perspectives in Biology·David H Perlmutter, Gary A Silverman
Feb 28, 2009·Annual Review of Biochemistry·Bibek Gooptu, David A Lomas
Oct 11, 2005·Annual Review of Cell and Developmental Biology·Karin Römisch
Dec 2, 2005·Neuroendocrinology·Dorien M de GrootGerard J M Martens
May 17, 2011·Journal of Translational Medicine·Raquel Rodríguez-GonzálezJosé Castillo
Mar 14, 2012·PloS One·Rosina NotoMauro Manno
Apr 12, 2014·Nature Communications·Zoe BudrikisStefano Zapperi
Jan 7, 2016·Scientific Reports·Giorgia SagaStefano Ricagno
Mar 7, 2009·Journal of Molecular Biology·Stefano RicagnoMartino Bolognesi
Nov 3, 2006·Current Opinion in Structural Biology·James C Whisstock, Stephen P Bottomley
Jun 29, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Elena MirandaDavid A Lomas
Jun 1, 2011·The FEBS Journal·Benoit D RousselDavid A Lomas
Dec 3, 2009·Protein Science : a Publication of the Protein Society·Didier BelorgeyDavid A Lomas
Apr 2, 2016·Journal of Hepatology·David A LomasBibek Gooptu
Apr 3, 2016·Brain Research·Navit Ogen-ShternGerardo Z Lederkremer
Oct 6, 2005·Trends in Cell Biology·Robin W Carrell
Dec 3, 2014·Revue des maladies respiratoires·A DuvoixD A Lomas
Sep 18, 2012·Biochimica Et Biophysica Acta·H WangD E Otzen
Apr 11, 2015·Frontiers in Neuroscience·Shinichi KondoZoltán Molnár
Apr 2, 2017·Free Radical Biology & Medicine·Lisa Vincenz-Donnelly, Mark S Hipp
Jan 16, 2008·Laboratory Investigation; a Journal of Technical Methods and Pathology·David Hernández-EspinosaJavier Corral
Mar 4, 2017·Scientific Reports·Costanza GiampietroCaterina A M La Porta
Nov 7, 2018·The Journal of Clinical Investigation·Didde HaslundJacob Giehm Mikkelsen

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.