ETL, a novel seven-transmembrane receptor that is Developmentally regulated in the heart - ETL is a member of the secretin family and belongs to the epidermal growth factor seven-transmembrane subfamily

Using differential display of rat fetal and postnatal cardiomyocytes, we ha ve identified a novel seven-trans-membrane receptor, ETL. The cDNA-predicte d amino acid sequence of ETL indicated that it encodes a 738-aa protein com posed of a large extracellular domain with epidermal growth factor (EGF)-li ke repeats, a seven-transmembrane domain, and a short cytoplasmic tail. ETL belongs to the secretin family of G-protein-coupled peptide hormone recept ors and the EGF-TM7 subfamily of receptors. The latter are characterized by a variable number of extracellular EGF and cell surface domains and conser ved seven transmembrane-spanning regions. ETL mRNA expression is up-regulat ed in the adult rat and human heart. In situ hybridization analyses reveale d expression in rat cardiomyocytes and abundant expression in vascular and bronchiolar smooth muscle cells. In COS-7 cells transfected with Myc-tagged rat ETL, rat ETL exists as a stable dimer and undergoes endoproteolytic cl eavage of the extracellular domain. The proteolytic activity can be abolish ed by a specific mutation, T455A, in this domain. In transfected mammalian cells, ETL is associated with cell membranes and is also observed in cytopl asmic: vesicles. ETL is the first seven-transmembrane receptor containing E GF-like repeats that is developmentally regulated in the heart.