Aquaporin CHIP: The archetypal molecular water channel

P. Agre, G. M. Preston, B. L. Smith, Sup Jung Jin Sup Jung, S. Raina, C. Moon, W. B. Guggino, S. Nielsen

Research output: Contribution to journalReview articlepeer-review


Despite longstanding interest by nephrologists and physiologists, the molecular identities of membrane water channels remained elusive until recognition of CHIP, a 28-kDa channel-forming integral membrane protein from human red blood cells originally referred to as 'CHIP28.' CHIP functions as an osmotically driven, water-selective pore; 1) expression of CHIP conferred Xenopus oocytes with markedly increased osmotic water permeability but did not allow transmembrane passage of ions or other small molecules; 2) reconstitution of highly purified CHIP into proteoliposomes permitted determination of the unit water permeability, i.e., 3.9 x 109 water molecules · channel subunit-1 · s-1. Although CHIP exists as a homotetramer in the native red blood cell membrane, site-directed mutagenesis studies suggested that each subunit contains an individually functional pore that may be reversibly occluded by mercurial inhibitors reacting with cysteine-189. CHIP is a major component of both apical and basolateral membranes of water-permeable segments of the nephron, where it facilitates transcellular water flow during reabsorption of glomerular filtrate. CHIP is also abundant in certain other absorptive or secretory epithelia, including choroid plexus, ciliary body of the eye, hepatobiliary ductules, gall bladder, and capillary endothelia. Distinct patterns of CHIP expression occur at these sites during fetal development and maturity. Similar proteins from other mammalian tissues and plants were later shown to transport water, and the group is now referred to as the 'aquaporins.' Recognition of CHIP has provided molecular insight into the biological phenomenon of osmotic water movement, and it is hoped that pharmacological modulation of CHIP function may provide novel treatments of renal failure and other clinical problems.

Original languageEnglish (US)
Pages (from-to)F463-F476
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number4 34-4
StatePublished - 1993


  • channel-forming integral membrane proteins
  • channel-mediated water transport
  • cysteine
  • fetal development
  • osmotic water permeability
  • water channels

ASJC Scopus subject areas

  • Physiology


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