이차 수정체 섬유세포 분화 과정에서 Sorting nexin 5의 역할

Abstract

Sorting nexin 5 (Snx5) has been known as a member of retromer complex, required for recycling of proteins back to cell membrane through Trans-Golgi-Network. Snx5 has a PX (Phospoinositide-binding structural) domain in its N-terminal and a BAR (Bin, Amphiphysin, Rvs) domain in its C-terminal. In general, Snx5 binds to phosphatidylinositol-3-monophosphate (PtdIns3P) with its PX domain and makes curvature of membrane with BAR domain. Through this interaction, Snx5 helps a separation of vesicles from endosomal compartment to pass through trans-golgi-network (TGN). In lens development, reciprocal interactions between ligands and receptors play crucial roles. Indeed, several receptor-mediated events affect each process of lens development. Growth factors signalings are typical examples, such as bone morphogenetic protein (BMP), basic fibroblast growth factor (bFgf), and epidermal growth factor (Egf). However, it is largely unknown how those receptor levels are regulated. Here, I show that the ablation of Snx5, a member of retromer complex, induces a cataract formation in lens of Snx5-/- mice. Histological analysis revealed that Snx5-/- mice have defective equatorial region of lens and abnormal differentiating secondary lens fiber. Also, the depletion of Snx5 resulted in overexpression of α-smooth muscle actin (α-SMA) in equatorial region of lens. Taken together, I propose that Snx5 gene plays an important role in trans-differentiation of lens fiber cells and cataract formation.