Ihog家族蛋白对整联蛋白功能的调节机制研究

整联蛋白在后口动物中是高度保守的，介导细胞黏着以进行信号转导，参与众多细胞过程，在胚胎发育、组织形成和稳态维持中起至关重要的作用，与癌症、自身免疫病等有密切关系。尽管对整联蛋白介导的黏着斑形成及相关蛋白已有大量研究，但“整联蛋白介导的细胞黏着是如何被调节的” 这个关键的基础生物学问题仍有许多机制尚未明确。申请人以果蝇为模式生物，发现Hedgehog信号转导中作为受体Ptc辅受体的Ihog家族蛋白的功能丧失能导致果蝇中整联蛋白缺陷的经典“膜泡”翅膀。本项目以此为基础，提出Ihog家族蛋白参与整联蛋白介导的细胞过程，从组织/细胞水平以及分子水平研究其对整联蛋白介导的细胞黏着的调节作用。本项目的实施，将有助于加深对整联蛋白介导的细胞黏着这一生物学过程的理解，为相关的人类疾病的诊断和治疗提供重要的理论基础和实践指导。

Integrins are well conserved in metazoan, mediating cell adhesion and the subsequent signal transduction for various cellular processes, and thus playing essential roles from embryonic development, organogenesis to tissue homeostasis maintenance, and being highly relevant to human diseases such as cancers and autoimmune diseases. Although our knowledge of the focal adhesion formation and the involved integrin associated proteins is ever expanding, the current understanding of the mechanisms on how the integrin-mediated focal adhesion is regulated, a key and fundamental question in biology, is way from satisfactory. Using Drosophila melanogaster as a model system, we discovered that the loss of Ihog proteins, the Patch co-receptors in Hedgehog signaling, leads to wing blister, a typical phenotype for integrin defects in Drosophila. In this proposal, we will further demonstrate the involvement of Ihog proteins in integrin biology and mechanistically explore their regulatory roles on integrin activation, clustering and the eventual focal adhesion formation from tissue/cellular level and molecular level. The outcomes of this project will improve the understanding of the biology underlying the integrin-mediated focal adhesion, providing new insights into the diagnosis and medical treatment of the related human diseases.