Show simple item record

dc.contributor.authorZainelli, Gina M.
dc.contributor.authorRoss, Christopher A.
dc.contributor.authorTroncoso, Juan C.
dc.contributor.authorFitzgerald, John K.
dc.contributor.authorMuma, Nancy A.
dc.date.accessioned2015-05-11T18:37:24Z
dc.date.available2015-05-11T18:37:24Z
dc.date.issued2004-02-25
dc.identifier.citationZainelli, G. M., Ross, C. A., Trsoncoso, J. C., Fitzgerald, J. K. & Muma, N.A. (2004) Calmodulin regulates transglutaminase 2 cross-linking of Huntingtin. The Journal for Neuroscience, 24(8), 1954-1961. http://www.dx.doi.org/10.1523/JNEUROSCI.4424-03.2004en_US
dc.identifier.urihttp://hdl.handle.net/1808/17700
dc.descriptionThis is the publisher's version, also available electronically from "www.jneurosci.org".en_US
dc.description.abstractStriatal and cortical intranuclear inclusions and cytoplasmic aggregates of mutant huntingtin are prominent neuropathological hallmarks of Huntington's disease (HD). We demonstrated previously that transglutaminase 2 cross-links mutant huntingtin in cells in culture and demonstrated the presence of transglutaminase-catalyzed cross-links in the HD cortex that colocalize with transglutaminase 2 and huntingtin. Because calmodulin regulates transglutaminase activity in erythrocytes, platelets, and the gizzard, we hypothesized that calmodulin increases cross-linking of huntingtin in the HD brain. We found that calmodulin colocalizes at the confocal level with transglutaminase 2 and with huntingtin in HD intranuclear inclusions. Calmodulin coimmunoprecipitates with transglutaminase 2 and huntingtin in cells transfected with myc-tagged N-terminal huntingtin fragments containing 148 polyglutamine repeats (htt-N63-148Q-myc) and transglutaminase 2 but not in cells transfected with myc-tagged N-terminal huntingtin fragments containing 18 polyglutamine repeats. Our previous studies demonstrated that transfection with both htt-N63-148Q-myc and transglutaminase 2 resulted in cross-linking of mutant huntingtin protein fragments and the formation of insoluble high-molecular-weight aggregates of huntingtin protein fragments. Transfection with transglutaminase 2 and htt-N63-148Q-myc followed by treatment of cells with N-(6-aminohexyl)-1-naphthalenesulfonamide, a calmodulin inhibitor, resulted in a decrease in cross-linked huntingtin. Inhibiting the interaction of calmodulin with transglutaminase and huntingtin protein could decrease cross-linking and diminish huntingtin aggregate formation in the HD brain.en_US
dc.publisherSociety for Neuroscienceen_US
dc.subjectcalmodulinen_US
dc.subjectHuntingtonen_US
dc.subjecttransglutaminaseen_US
dc.subjectprotein aggregationen_US
dc.subjectinclusion bodiesen_US
dc.subjectcross-linkingen_US
dc.titleCalmodulin regulates transglutaminase 2 cross-linking of Huntingtinen_US
dc.typeArticle
kusw.kuauthorMuma, Nancy A.
kusw.kudepartmentPharmacology & Toxicologyen_US
dc.identifier.doi10.1523/JNEUROSCI.4424-03.2004
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record