Blood Journal
Leading the way in experimental and clinical research in hematology

Isolation of cDNA coding for an ubiquitous membrane protein deficient in high Na+, low K+ stomatocytic erythrocytes

  1. GW Stewart,
  2. BE Hepworth-Jones,
  3. JN Keen,
  4. BC Dash,
  5. AC Argent, and
  6. CM Casimir
  1. Department of Medicine, University College and Middlesex Medical School, Rayne Institute, London, UK.

Abstract

Human red blood cells (RBCs) that are deficient in an integral membrane- associated protein (“stomatin“) of apparent molecular mass 31 Kd show a catastrophic increase in passive membrane permeability to the univalent cations Na+ and K+ and are stomatocytic in shape. We have purified this protein from normal RBC membranes and isolated a cDNA clone coding for it. The deduced protein sequence is unrelated to that of any known ion- transport-related protein. Selective solubilization studies using detergents show that while the protein is strongly associated with the phospholipid bilayer, it also binds to the cytoskeleton. The predicted polypeptide has a single trans-membranous hydrophobic segment near the N-terminus, which would locate it in the membrane; the large C-terminal domain is hydrophilic and cytoplasmic in orientation and is presumed to be responsible for the attachment to the cytoskeleton. By inference, the protein has the function of closing a latent ion channel. The messenger RNA encoding this protein is ubiquitously distributed in different human cell types and tissues and is thus presumably a widely distributed regulator of transmembrane cation fluxes. As a membrane- bound inhibitor protein of Na+ and K+ transport, it is unique among the known components of membrane-transport proteins.