Anavex Life Sciences Corp (AVXL)

[georgejjl]

Jimmy:

Sigma-1 Receptor
The ER chaperone proteins known as sigma receptors are targets for certain neurosteroids. Based on their biochemical and pharmacological properties, two subclasses, sigma-1 and sigma-2 receptors, are distinguished but only the sigma-1 receptor was cloned and properly characterized [57, 58]. The sigma-1 receptor is involved in many physiological functions as well as in several pathological conditions [58].

Sigma-1 receptors are especially enriched at the MAMs [59]. A specific interaction between the Ca2+-binding chaperone BiP and the sigma-1 receptor was described [59]. This interaction depends on the ER Ca2+ concentration: a decrease in ER Ca2+ concentration leads to their dissociation, whereby both proteins become active chaperones.

The sigma-1 receptor regulates several ion channels, including the IP3Rs [58]. Agonists of sigma-1 receptors could so potentiate agonist-induced Ca2+ release in NG108 cells [60]. Hereby, an interaction between the sigma-1 receptor, cytoskeletal ankyrin B, and IP3R3 was demonstrated [61]. In CHO cells, the sigma-1 receptor also interacted with IP3R3, but here ankyrin was not observed in the complex. Finally, a specific role was found for the sigma-1 receptor stabilizing the IP3R3 present at the MAMs, and so regulating Ca2+ transfer between ER and mitochondria.

https://www.hindawi.com/journals/jar/2011/920178/

In conclusion, our results constitute the first report that
the mitochondrial Ca2+ signaling can be controlled by
chaperone machineries on the side of the ER and that
the unique receptor chaperone Sig-1R plays important
roles in the ER-mitochondrial interorganelle Ca2+ signaling
and in cell survival as well.[/color]

https://www.cell.com/action/showPdf?pii=S0092-8674%2807%2901099-9