The Neuronal Adaptor Protein X11α Interacts with the Copper Chaperone for SOD1 and Regulates SOD1 Activity

• Published in: The Journal of biological chemistry 2001-03, Vol.276 (12), p.9303-9307
• Main Authors: McLoughlin, Declan M., Standen, Claire L., Lau, Kwok-Fai, Ackerley, Steven, Bartnikas, Thomas P., Gitlin, Jonathan D., Miller, ChristopherC.J.
• Format: Article
• Language: English
• Subjects: neuronal adaptor protein X11^a
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M010023200

The neuronal adaptor protein X11α participates in the formation of multiprotein complexes and intracellular trafficking. It contains a series of discrete protein-protein interaction domains including two contiguous C-terminal PDZ domains. We used the yeast two-hybrid system to screen for proteins that interact with the PDZ domains of human X11α, and we isolated a clone encoding domains II and III of the copper chaperone for Cu,Zn-superoxide dismutase-1 (CCS). The X11α/CCS interaction was confirmed in coimmunoprecipitation studies plus glutathioneS-transferase fusion protein pull-down assays and was shown to be mediated via PDZ2 of X11α and a sequence within the carboxyl terminus of domain III of CCS. CCS delivers the copper cofactor to the antioxidant superoxide dismutase-1 (SOD1) enzyme and is required for its activity. Overexpression of X11α inhibited SOD1 activity in transfected Chinese hamster ovary cells which suggests that X11α binding to CCS is inhibitory to SOD1 activation. X11α also interacts with another copper-binding protein found in neurons, the Alzheimer's disease amyloid precursor protein. Thus, X11α may participate in copper homeostasis within neurons.