SPLICE VARIANTS OF THE HA RECEPTOR FOR ENDOCYTOSIS

用于内吞作用的 HA 受体的剪接变体

• 批准号: 6936749
• 负责人: EDWARD N HARRIS
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936749
• 关键词: RNA splicing; animal tissue; antibody; carbohydrate metabolism; chondroitin sulfates; clinical research; endocytosis; gene expression; heparin; human tissue; hyaluronate; mucopolysaccharides; neural cell adhesion molecules; postdoctoral investigator; protein isoforms; protein purification; tissue /cell culture

DESCRIPTION (provided by applicant): Hyaluronic acid is a large dynamic glycosaminoglycan (GAG), which plays an important role in the extracellular matrix, cell signalling, organ development, wound healing and cell motility. The human hyaluronic acid (HA) receptor for endocytosis (HARE/Stab2) is encoded by a 180227 bp gene consisting of 69 exons. This type 1 receptor is the only known HA receptor to bind and internalize HA and Chondroitin Sulfates (CS) though clathrin-mediated endocytosis. Due to the number of exons in the gene, we hypothesize that multiple mRNA species encoding functionally distinct hHARE variants arise through gene splicing. The primary goals of this project are to identify and characterize HARE/Stab2 splice variants and determine their potential impact on GAG homeostasis. The project is divided into 3 specific aims which are; 1) to continue screening cDNA pools from human tissues for splice variants, 2) to assess GAG binding activity of stably expressed HARE splice variants in cell culture and binding assays, and 3) determine what splice variants are expressed in adult developed and undeveloped human tissues. The significance of HARE isoforms is the potential to create a family of receptors that bind/internalize a host of different GAGs.

描述（由申请人提供）： 透明质酸是一种大的动态糖胺聚糖（GAG），其在细胞外基质、细胞信号传导、器官发育、伤口愈合和细胞运动中起重要作用。人透明质酸（HA）胞吞受体（HARE/Stab 2）基因全长180227 bp，由69个外显子组成。这种1型受体是唯一已知的通过网格蛋白介导的内吞作用结合和内化HA和硫酸软骨素（CS）的HA受体。由于基因中外显子的数量，我们假设多个mRNA种类编码功能不同的hHARE变体通过基因剪接产生。本项目的主要目标是鉴定和表征HARE/Stab 2剪接变体，并确定其对GAG稳态的潜在影响。该项目分为3个具体目标，即：1）继续从人类组织中筛选剪接变体的cDNA库，2）在细胞培养和结合试验中评估稳定表达的HARE剪接变体的GAG结合活性，3）确定在成人发育和未发育的人类组织中表达何种剪接变体。HARE同种型的重要性在于产生结合/内化不同GAG的宿主的受体家族的潜力。