dc.contributor.author | Zainelli, Gina M. | |
dc.contributor.author | Ross, Christopher A. | |
dc.contributor.author | Troncoso, Juan C. | |
dc.contributor.author | Fitzgerald, John K. | |
dc.contributor.author | Muma, Nancy A. | |
dc.date.accessioned | 2015-05-11T18:37:24Z | |
dc.date.available | 2015-05-11T18:37:24Z | |
dc.date.issued | 2004-02-25 | |
dc.identifier.citation | Zainelli, 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.4424-03.2004 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17700 | |
dc.description | This is the publisher's version, also available electronically from "www.jneurosci.org". | en_US |
dc.description.abstract | Striatal 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.publisher | Society for Neuroscience | en_US |
dc.subject | calmodulin | en_US |
dc.subject | Huntington | en_US |
dc.subject | transglutaminase | en_US |
dc.subject | protein aggregation | en_US |
dc.subject | inclusion bodies | en_US |
dc.subject | cross-linking | en_US |
dc.title | Calmodulin regulates transglutaminase 2 cross-linking of Huntingtin | en_US |
dc.type | Article | |
kusw.kuauthor | Muma, Nancy A. | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
dc.identifier.doi | 10.1523/JNEUROSCI.4424-03.2004 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess | |