The molecular structure of the antidiuretic hormone elicited water channel.
Measurements of osmotic water permeability (Pf) have shown that the plasma membranes of human red cells and certain epithelial cells possess specialized water channels. Although these water channels have been characterized extensively using biophysical techniques, the proteins that compose these unique channels have only recently been identified. Antidiuretic hormone (ADH) stimulation rapidly increases collecting duct epithelial cell Pf by fusion of water channel-containing vesicles (WCV) with their apical membranes. The proteins of WCV from toad bladder and rodent kidney have been characterized. The principal proteins in toad bladder WCV are 55,000 daltons (55 kDa) and 53 kDa and span the lipid bilayer of these vesicles. Polyclonal antisera raised against the 55-kDa and 53-kDa proteins inhibit ADH-stimulated toad bladder Pf by 80% and recognize protein bands of 46, 38 and 30 kDa in mouse kidney. Purification of WCV from rat kidney reveals enrichment of the 46-kDa protein. Recently, a 28-kDa integral membrane protein (called CHIP-28) has been isolated from human red cells. It forms functional water channels in Xenopus oocytes and when reconstituted into proteoliposomes. Large amounts of CHIP-28 protein are present in epithelial cells of the proximal tubule and descending thin limb of Henle's loop. Molecular cloning efforts are underway to elucidate the structure and function of these candidate water channel proteins.
Harris
H W
HW
Division of Nephrology, Children's Hospital, Boston, MA 02115.
Paredes
A
A
Zeidel
M L
ML
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D001789:Blood Group Antigens; D002463:Cell Membrane Permeability; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014667:Vasopressins / Q000494:pharmacology*; D014867:Water / Q000378:metabolism*
C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D007473:Ion Channels; D008565:Membrane Proteins; D014867:Water; D014667:Vasopressins; D051398:Aquaporin 1