講演情報
[O2-1]若年性遺伝子BEX1は一次繊毛の形成に必須な天然変性タンパク質をコードする
○森 雅樹 (国立循環器病研究センター研究所 血管生理学部)
Children possess numerous advantages that adults do not. These advantages include properties of organ size control, maturation, learning, recovery, and others. The underlying mechanism for the children’s advantages is not fully understood. We identified juvenility-associated genes (JAGs) as building blocks for the children’s inherent properties. We show a new role for BEX1, a JAG, that was widely expressed in juvenile organs. Subcellular localization studies reveal that BEX1 localizes to the basal body in a cell density-dependent manner and is indispensable for primary cilia formation. Bex1 knockout mice exhibit loss of primary cilia at retinal pigment epithelium (RPE) and striatum. The Bex1 mutant mice present ciliopathy phenotypes, including malformation of RPE, polycystic kidney disease, and cerebellar hypoplasia. The constellation of the symptoms implied the manifestations were similar to those observed in Joubert syndrome. Circular dichroism and nuclear magnetic resonant (NMR) spectroscopies reveal that BEX1 harbors the properties of being an intrinsically disordered protein (IDP). NMR spectroscopies revealed that BEX1 protein bound to GTP, the energy substrate for tubulin polymerization. Recombinant BEX1 protein can form the biomolecular concentrates that facilitate tubulin polymerization in the reconstituted system. Thus, we demonstrate that BEX1 possesses physicochemical properties as IDP and provides a reaction field at the ciliary bases that are indispensable for ciliogenesis.