Sci. STKE, 23 January 2001
Calcium Ankyrin Away
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.
Citation: Ankyrin Away. Sci. STKE 2001, tw5 (2001).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882