SPLICE VARIANTS OF THE HA RECEPTOR FOR ENDOCYTOSIS

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.