The role of calmodulin recruitment in Ca2+ stimulation of adenylyl cyclase type 8.

The Journal of Biological Chemistry
Rachel E SimpsonDermot M F Cooper

Abstract

Ca2+ stimulation of adenylyl cyclase type 8 (AC8) is mediated by calmodulin (CaM). An earlier study identified two CaM binding sites in AC8; one that was apparently not essential for AC8 activity, located at the N terminus, and a second site that was critical for Ca2+ stimulation, found at the C terminus (Gu, C., and Cooper, D. M. F. (1999) J. Biol. Chem. 274, 8012-8021). This study explores the role of these two CaM binding domains and their interaction in regulating AC8 activity, employing binding and functional studies with mutant CaM and modified AC8 species. We report that the N-terminal CaM binding domain of AC8 has a role in recruiting CaM and that this recruitment is essential to permit stimulation by Ca2+ in vivo. Using Ca2+-insensitive mutants of CaM, we found that partially liganded CaM can bind to AC8, but only fully liganded Ca2+/CaM can stimulate AC8 activity. Moreover, partially liganded CaM inhibited AC8 activity in vivo. The results indicate that CaM pre-associates with the N terminus of AC8, and we suggest that this recruited CaM is used by the C terminus of AC8 to mediate Ca2+ stimulation.

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Citations

Sep 28, 2013·Analytical and Bioanalytical Chemistry·Sabine HerbstAndrea Sinz
Oct 4, 2012·Nature Cell Biology·Katleen Lemaire, Frans Schuit
Apr 23, 2010·The Journal of Biological Chemistry·Debbie WilloughbyDermot M F Cooper
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Apr 13, 2012·Science Signaling·Debbie WilloughbyDermot M F Cooper
Jan 23, 2009·American Journal of Physiology. Cell Physiology·Mario PaganoDermot M F Cooper
May 28, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hong XuJonathan A Raper
May 16, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mario StrazzaboscoGianfranco Alpini
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Aug 8, 2014·The Biochemical Journal·Dermot M F Cooper, Valentina G Tabbasum
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Oct 17, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Rebecca A CapelDerek A Terrar
Sep 14, 2012·Biochemistry·Nanako MasadaDermot M F Cooper

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