Polycystin-1L2 is a novel G-protein-binding protein

Genomics. 2004 Jul;84(1):126-38. doi: 10.1016/j.ygeno.2004.02.008.

Abstract

Mutations in genes encoding polycystin-1 (PC1) and polycystin-2 cause autosomal dominant polycystic kidney disease. The polycystin protein family is composed of Ca2+-permeable pore-forming subunits and receptor-like integral membrane proteins. Here we describe a novel member of the polycystin-1-like subfamily, polycystin-1L2 (PC1L2), encoded by PKD1L2, which has various alternative splicing forms with two translation initiation sites. PC1L2 short form starts in exon 12 of the long form. The longest open reading frame of PKD1L2 short form, determined from human testis cDNA, encodes a 1775-amino-acid protein and 32 exons, whereas the long form is predicted to encode a 2460-residue protein. Both forms have a small receptor for egg jelly domain, a G-protein-coupled receptor proteolytic site, an LH2/PLAT, and 11 putative transmembrane domains, as well as a number of rhodopsin-like G-protein-coupled receptor signatures. RT-PCR analysis shows that the short form, but not the long form, of human PKD1L2 is expressed in the developing and adult heart and kidney. Furthermore, by GST pull-down assay we observed that PC1L2 and polycystin-1L1 are able to bind to specific G-protein subunits. We also show that PC1 C-terminal cytosolic domain binds to Galpha12, Galphas, and Galphai1, while it weakly interacts with Galphai2. Our results indicate that both PC1-like molecules may act as G-protein-coupled receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / genetics*
  • Alternative Splicing / physiology
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • Humans
  • Kidney / metabolism*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Organ Specificity / genetics
  • Organ Specificity / physiology
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Proteins / genetics*
  • Proteins / metabolism
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism*
  • Sequence Alignment
  • TRPP Cation Channels
  • Transcription, Genetic / genetics

Substances

  • Membrane Proteins
  • PKD1L2 protein, human
  • Proteins
  • Receptors, G-Protein-Coupled
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • GTP-Binding Proteins
  • Calcium