The PLAT domain: a new piece in the PKD1 puzzle

Südhof TC: α α-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. requirements for α α-latrotoxin binding and α α-latrotoxin-stimulated secretion. α α-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. AG: A novel ubiquitously expressed α α-latrotoxin receptor is a member of the CIRL family of G-protein-coupled receptors. CD97 is a processed, seven-transmembrane, heterodimeric receptor associated with inflammation. pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection. Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains. sea urchin sperm receptor for egg jelly is a modular protein with extensive homology to the human polycystic kidney disease protein, PKD1. Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Identification of a human homologue of the sea urchin receptor for egg jelly: a polycystic kidney disease-like protein. a gene for polycystic kidney disease that encodes an integral membrane protein. Autosomal dominant polycystic kidney disease (ADPKD) has a prevalence of 1 in 800 of the world's population and accounts for 10% of individuals who require renal replacement therapy, either dialysis or transplantation. Renal cyst formation occurs as part of a 'two-hit' process in which inactivation of both alleles of ADPKD genes leads to abnormalities of cell proliferation, apoptosis and differentiation [1]. Of ADPKD cases, 85% are due to mutations in the PKD1 gene, which encodes a 4,302 amino acid protein, polycystin-1 (PKD1), of unknown function. Comparison of the PKD1 sequence with homologous sequences from mouse and Fugu predicts polycystin-1 to have a large extracellular region of 3,000 amino acid residues, a region containing 11 putative transmembrane segments and a short intracellular tail [2]. A well-defined extracellular domain structure is apparent; the presence of amino-terminal leucine-rich repeats, a C-type-lectin domain and multiple PKD repeats suggests a role in cell–cell or cell–matrix interactions (Figure 1) [3]. So far, no extracellular ligands of polycystin-1 have been identified. Of the intracellular regions of PKD1, functional properties have been defined only for the short 198 amino acid carboxy-terminal region, which contains a predicted coiled-coil domain. These include a direct interaction with the carboxyl terminus of the protein encoded by PKD2, polycystin-2 [4], activation of Schematic diagram of the domain organisation of PLAT domain proteins. Information and alignments for each of the domains can be …