The relevance of chorein for FGF23 production and Ca2+/phosphate metabolism

点击翻译按钮获取中文摘要

Fibroblast growth factor 23 (FGF23) is produced by bone cells andinhibits renal phosphate reabsorption and formation of calcitriol,biologically active vitamin D, along with its obligatory co-receptorKlotho. FGF23 or Klotho deficiency result in rapid aging, a short lifespan, and the onset of a plethora of aging-associated diseases. Anincrease in FGF23 levels is observed in many acute and chronichuman disorders. The regulation of FGF23 synthesis on a cellularlevel is ill-defined. Chorein is a protein expressed in different tissues.Chorein deficiency or malfunction lead to chorea-acanthocytosis, arare genetic disorder characterized by abnormal movements andacanthocytes, misshaped erythrocytes. Cellular functions of choreinare incompletely understood. According to our published studieschorein regulates the polymerization of actin cytoskeleton. Moreover,the reorganization of the actin cytoskeleton affects FGF23 production.The present project aims at elucidating (i) the cellular and molecularmechanisms of chorein-dependent FGF23 formation, (ii) thephysiological relevance of chorein for Ca2+/phosphate metabolism,calcitriol synthesis and vascular calcification, and (iii) the impact ofchorein on renal and intestinael membrane transport. The project isexpected to uncover novel cellular functions of chorein. Moreover, itwill identify novel regulators of FGF23. This will contribute to a betterunderstanding of the physiological and pathophysiological role ofFGF23.