DISCS-LOST IN APICAL CELL JUNCTIONS IN DROSOPHILA EYE

果蝇眼顶端细胞连接处的圆盘丢失

• 批准号: 6684460
• 负责人: Kwang-Wook Choi
• 金额: $ 30.1万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-07 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6684460
• 关键词: Drosophilidae; apical membrane; arthropod genetics; biological signal transduction; cell differentiation; cellular polarity; cytoskeleton; developmental genetics; fluorescence resonance energy transfer; gene mutation; gene targeting; genetic models; intercellular connection; intracellular transport; invertebrate embryology; membrane proteins; neurogenesis; protein kinase C; protein localization; protein protein interaction; protein structure function; retina; visual photoreceptor

DESCRIPTION (provided by applicant): Apico-basal cell polarity is essential for epithelial morphogenesis. Retinal differentiation involves dynamic process of cell-cell interactions and junctional organizations. The Drosophila compound eye provides an excellent gentic model for studying such cellular processes. A hallmark of photoreceptor differentiation is an explosive growth of the photosensitive organ, or rhabdomere, in the apical cell membrane. Drosophila Crumbs (Crb) protein plays a key role in organizing the rhabdomere and adherens junction (AJ) of photoreceptors. Our goal is to dissect the molecular basis of Crb function in the photoreceptor morphogenesis. Crb is a transmembrane protein with a short cytoplasmic tail. This intracellular domain (Crb intra) can recruit a MAGUK family protein Stardust (Sdt) and a PDZ domain protein Discs-lost (Dlt) to form a protein complex. An important function of Crb complex is to recruit AJs and to induce and/or maintain growth of rhabdomeres. Another conserved protein complex composed of Bazooka, Par6 and atypical PKC (aPKC) is critical for epithelial polarity. Interestingly, Par6 colocalizes and directly interacts with Dlt at the apical membrane. A novel Dlt homolog, Dlt-like (Dlk), also directly binds Par6. Therefore, it is proposed that Dlt and Dlk may regulate the cross-talk between the Crb and Par complexes. To test this hypothesis, the function of Crb and Par complexes in photoreceptor morphogenesis will be analyzed by genetic, molecular and cytochemical methods. Whether Dlt and Dlk are required for Crb and Par functions will be addressed. Specific interaction domains of Dlt and Dlk and their functions in the Par complex will be examined. In addition, specific proteins involved in trafficking of cytoskeletons to the Crb and Par complexes will be identified to understand the mechanism of AJ formation. Drosophila and human Crb proteins are conserved in structure and function. Human CRB1 is associated with retinal diseases including retinitis pigmentosa 12 and Leber Congenital Amaurosis. Therefore, studies on novel interaction of Crb and Par complexes will provide important insights into the mechanism of human CRB 1 in normal retinal development and diseases associated with CRB1 mutations.

描述（由申请人提供）：顶基细胞极性对上皮形态发生至关重要。视网膜分化涉及细胞间相互作用和连接组织的动态过程。果蝇复眼为研究这类细胞过程提供了一个极好的遗传模型。光感受器分化的一个标志是顶端细胞膜上光敏器官或横纹肌的爆炸性生长。果蝇碎屑蛋白（Drosophila crumb, Crb）在组织光感受器横纹肌和粘附体连接（AJ）中起关键作用。我们的目标是剖析Crb在光感受器形态发生中的功能的分子基础。