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Sci. Signal., 11 September 2012
Vol. 5, Issue 241, p. ra67
[DOI: 10.1126/scisignal.2002700]

RESEARCH ARTICLES

Editor's Summary

Moving the Catalytic Domain to the Inside
CD38 is a membrane-bound enzyme that catalyzes both the production and the hydrolysis of cyclic ADP ribose (cADPR), an intracellular messenger that stimulates the release of Ca2+ from the endoplasmic reticulum. However, CD38 is thought to exist as a type II transmembrane protein with its C-terminal catalytic domain on the outside of the cell; thus, how it contributes to intracellular signaling is controversial. With antibodies specific for the N-terminal region of CD38, Zhao et al. showed in cell lines and primary human cells the presence of a proportion of CD38 in the type III form, with the catalytic domain facing the cytosol. Mutations in the N-terminal region of CD38 flipped its orientation in the membrane so that it was only present in the type III form, and transfected cells expressing this mutant were more efficient at producing cADPR than were cells expressing wild-type CD38. Together, these data suggest that cells have CD38 molecules in opposing orientations, with the type III form predominantly responsible for signaling.

Citation: Y. J. Zhao, C. M. C. Lam, H. C. Lee, The Membrane-Bound Enzyme CD38 Exists in Two Opposing Orientations. Sci. Signal. 5, ra67 (2012).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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In vitro reconstitution of lipid-dependent dual topology and postassembly topological switching of a membrane protein.
H. Vitrac, M. Bogdanov, and W. Dowhan (2013)
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