ISOLATION AND CHARACTERIZATION OF STANNIOCALCIN-1 RECEPTOR IN FISH GILLS OF JAPANESE EELS.

Calcium ion is vital for many cellular and physiological processes which are critical in life. The maintenance of Ca2+ homeostasis in cellular and extracellular compartments is coordinated via the actions of hormones and their effects on intestinal Ca2+ absorption, renal reabsorption and bone resorption/absorption. Disorders of calcium metabolism can be the cause or consequences of many pathological symptoms and can be life-threatening. Although the regulatory mechanism in blood Ca2+ level has been thoroughly studied, our understanding on the regulation of cellular and mito- chondrial Ca2+ homeostasis in cell dysfunction and disease progression have not been fully eluci- dated. Recent advances have identified the involvement of a new mammalian factor stanniocalcin- 1 (STC1) in cellular and mitochondrial Ca2+ -regulation. The receptor of STC1 however, has not been cloned and hence an understanding on the function of the receptor is still missing. The iden- tification of STC1 receptor in mammals has long been proven to be challenging since the identity of its target cells is not known.

STC1 is a well-known fish hypocalcemic hormone that targets on gills to inhibit Ca2+ transport. This functional relationship has been known for decades, yet surprisingly, the STC1 receptor in fishes has also not been cloned. Different from the mammalian model, fish gill cells are a well- recognized target to the hormone. Our recent studies have demonstrated specific binding of STC1 on plasma membrane and mitochondria of gill cells. The binding was found to provoke elevation of the 2nd messenger cAMP and protect cells from Ca2+ -induced toxicity. The data provided solid evidences to support the notion that STC1 receptor is expressed in gills.

The gills of euryhaline fish are naturally exposed to waters of varying Ca2+ levels that impose a continuous control on Ca 2+ -regulatory mechanism. This makes it as an excellent biological tissue for the isolation of STC1 receptor and characterization of its post-receptor signaling cascades. In addition, it would be an important model to reveal the dynamic regulatory mechanism of epithelial Ca2+-transport and homeostasis in vertebrates. The success of the study will provide invaluable insights to help isolate and characterize the receptor in mammals. The outcome of this study will open up a new approach to investigate Ca2+ transport in fishes and reveal how this fundamental process evolves in mammals. This knowledge will ultimately lead to direct and profound impacts from the improvement of aquaculture practices to advances in biomedical research.