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

成纤维细胞生长因子23 （FGF23）由骨细胞产生，抑制肾磷酸再吸收和骨化三醇的形成，骨化三醇是一种生物活性维生素D，以及它的强制性共受体klotho。FGF23或Klotho缺乏导致快速衰老，寿命缩短，以及大量与衰老相关的疾病的发作。在许多急性和慢性人类疾病中观察到FGF23水平的升高。FGF23合成在细胞水平上的调控是不明确的。Chorein是一种在不同组织中表达的蛋白质。舞蹈病-棘细胞增多症是一种罕见的遗传性疾病，以异常运动和棘细胞、畸形红细胞为特征。舞蹈病的细胞功能尚不完全清楚。根据我们发表的研究，chorein调节肌动蛋白细胞骨架的聚合。此外，肌动蛋白骨架的重组影响FGF23的产生。目前的项目旨在阐明(i)依赖于chorein的FGF23形成的细胞和分子机制，（ii） chorein与Ca2+/磷酸盐代谢、骨化三醇合成和血管钙化的生理相关性，以及（iii） chorein对肾和肠膜运输的影响。该项目有望揭示舞蹈蛋白的新细胞功能。此外，它将确定FGF23的新调节因子。这将有助于更好地理解ofFGF23的生理和病理生理作用。

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.