Editors' ChoiceCalcium

Ankyrin Away

Science's STKE  23 Jan 2001:
Vol. 2001, Issue 66, pp. tw5
DOI: 10.1126/stke.2001.66.tw5

One mechanism for increasing [Ca2+]i is by release from the endoplasmic reticulum (ER) through the activation of inositol-1,4,5-trisphosphate receptors (IP3R). Hayashi and Su provide evidence that an interaction between the cytoskeletal adaptor ankyrin and sigma-1 receptors regulates the affinity of the IP3R for IP3 and thus, regulates intracellular calcium signaling. The authors show that the sigma-1 receptor, two isoforms of ankyrin (ANK220 and ANK135), and the IP3R exist in an ER-localized complex. Using pharmacological agonists and antagonists for the sigma-1 receptor, they provide evidence that activation of sigma-1 receptors enhances IP3 binding to its receptors by dissociating both the sigma receptor and ankyrin from the IP3R, and thus enhances IP3-mediated calcium signals. Sigma-1 receptor antagonists stabilize the ankyrin and IP3R complex, yet promote the dissociation of the sigma receptor from the complex. These data provide a mechanism for the effects of sigma receptor agonists, such as cocaine and neurosteroids, on calcium signaling.

T. Hayashi, T.-P. Su, Regulating ankyrin dynamics: Roles of sigma-1 receptors. Proc. Natl. Acad. Sci. U.S.A. 98, 491-496 (2001). [Abstract] [Full Text]