Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression.

Hdl Handle:
http://hdl.handle.net/10034/609046
Title:
Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression.
Authors:
Zatyka, Malgorzatta; Xavier, Gabriela Da Silva; Bellomo, Elisa A.; Leadbeater, Wendy; Astuti, Dewi; Smith, Joel; Michelangeli, Francesco; Rutter, Guy A.; Barrett, Timothy G.
Abstract:
Wolfram syndrome is an autosomal recessive disorder characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein that is involved in the regulation of the unfolded protein response (UPR), intracellular ion homeostasis, cyclic adenosine monophosphate production and regulation of insulin biosynthesis and secretion. In this study, single cell Ca(2+) imaging with fura-2 and direct measurements of free cytosolic ATP concentration ([ATP]CYT) with adenovirally expressed luciferase confirmed a reduced and delayed rise in cytosolic free Ca(2+) concentration ([Ca(2+)]CYT), and additionally, diminished [ATP]CYT rises in response to elevated glucose concentrations in WFS1-depleted MIN6 cells. We also observed that sarco(endo)plasmic reticulum ATPase (SERCA) expression was elevated in several WFS1-depleted cell models and primary islets. We demonstrated a novel interaction between WFS1 and SERCA by co-immunoprecipitation in Cos7 cells and with endogenous proteins in human neuroblastoma cells. This interaction was reduced when cells were treated with the ER stress inducer dithiothreitol. Treatment of WFS1-depleted neuroblastoma cells with the proteasome inhibitor MG132 resulted in reduced accumulation of SERCA levels compared with wild-type cells. Together these results reveal a role for WFS1 in the negative regulation of SERCA and provide further insights into the function of WFS1 in calcium homeostasis.
Affiliation:
University of Birmingham, Imperial College London,
Citation:
Zatyka, M., Xavier, G. D. S., Bellomo, E. A., Leadbeater, W., Astuti, D., Smith, J., Michelangeli, F., Rutter, G. A., Barrett, T. G. (2015). Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression. Human Molecular Genetics, 24(3), 814-27. http://dx.doi.org/10.1093/hmg/ddu499
Publisher:
Oxford University Press
Journal:
Human Molecular Genetics
Publication Date:
1-Feb-2015
URI:
http://hdl.handle.net/10034/609046
DOI:
10.1093/hmg/ddu499
Additional Links:
http://hmg.oxfordjournals.org/content/24/3/814.long
Type:
Article
Language:
en
Description:
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Zatyka, M., Xavier, G. D. S., Bellomo, E. A., Leadbeater, W., Astuti, D., Smith, J., Michelangeli, F., Rutter, G. A., Barrett, T. G. (2015). Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression. Human Molecular Genetics, 24(3), 814-27 is available online at: http://dx.doi.org/10.1093/hmg/ddu499
ISSN:
0964-6906
EISSN:
1460-2083
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorZatyka, Malgorzattaen
dc.contributor.authorXavier, Gabriela Da Silvaen
dc.contributor.authorBellomo, Elisa A.en
dc.contributor.authorLeadbeater, Wendyen
dc.contributor.authorAstuti, Dewien
dc.contributor.authorSmith, Joelen
dc.contributor.authorMichelangeli, Francescoen
dc.contributor.authorRutter, Guy A.en
dc.contributor.authorBarrett, Timothy G.en
dc.date.accessioned2016-05-11T11:44:23Zen
dc.date.available2016-05-11T11:44:23Zen
dc.date.issued2015-02-01en
dc.identifier.citationZatyka, M., Xavier, G. D. S., Bellomo, E. A., Leadbeater, W., Astuti, D., Smith, J., Michelangeli, F., Rutter, G. A., Barrett, T. G. (2015). Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression. Human Molecular Genetics, 24(3), 814-27. http://dx.doi.org/10.1093/hmg/ddu499en
dc.identifier.issn0964-6906en
dc.identifier.doi10.1093/hmg/ddu499en
dc.identifier.urihttp://hdl.handle.net/10034/609046en
dc.descriptionThis is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Zatyka, M., Xavier, G. D. S., Bellomo, E. A., Leadbeater, W., Astuti, D., Smith, J., Michelangeli, F., Rutter, G. A., Barrett, T. G. (2015). Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression. Human Molecular Genetics, 24(3), 814-27 is available online at: http://dx.doi.org/10.1093/hmg/ddu499en
dc.description.abstractWolfram syndrome is an autosomal recessive disorder characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein that is involved in the regulation of the unfolded protein response (UPR), intracellular ion homeostasis, cyclic adenosine monophosphate production and regulation of insulin biosynthesis and secretion. In this study, single cell Ca(2+) imaging with fura-2 and direct measurements of free cytosolic ATP concentration ([ATP]CYT) with adenovirally expressed luciferase confirmed a reduced and delayed rise in cytosolic free Ca(2+) concentration ([Ca(2+)]CYT), and additionally, diminished [ATP]CYT rises in response to elevated glucose concentrations in WFS1-depleted MIN6 cells. We also observed that sarco(endo)plasmic reticulum ATPase (SERCA) expression was elevated in several WFS1-depleted cell models and primary islets. We demonstrated a novel interaction between WFS1 and SERCA by co-immunoprecipitation in Cos7 cells and with endogenous proteins in human neuroblastoma cells. This interaction was reduced when cells were treated with the ER stress inducer dithiothreitol. Treatment of WFS1-depleted neuroblastoma cells with the proteasome inhibitor MG132 resulted in reduced accumulation of SERCA levels compared with wild-type cells. Together these results reveal a role for WFS1 in the negative regulation of SERCA and provide further insights into the function of WFS1 in calcium homeostasis.en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urlhttp://hmg.oxfordjournals.org/content/24/3/814.longen
dc.subjectbiochemistryen
dc.subjectmolecular medicineen
dc.titleSarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression.en
dc.typeArticleen
dc.identifier.eissn1460-2083en
dc.contributor.departmentUniversity of Birmingham, Imperial College London,en
dc.identifier.journalHuman Molecular Geneticsen
dc.date.accepted2014-09-26en
or.grant.openaccessYesen
rioxxterms.funderunfundeden
rioxxterms.identifier.projectunfunded researchen
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2016-05-11en
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