Aquaporin - Discovery

Discovery

Agre said he discovered aquaporins "by serendipity." His lab had an N.I.H. grant to study the Rh blood group antigen. They isolated the Rh molecule but a second molecule, 28 kilodaltons in size (and therefore called 28K) kept appearing. At first they thought it was a piece of the Rh molecule, or a contaminant, but it turned out to be an undiscovered molecule with unknown function. It was abundant in red blood cells and kidney tubes, and related to proteins of diverse origins, like the brains of fruit flies, bacteria, the lenses of eyes, and plant tissues.

In most cells, water moves in and out by osmosis through the lipid component of cell membranes. Due to the relatively high water permeability of some epithelial cells it was long suspected that some additional mechanism for water transport across membranes must exist. But it was not until 1992 that the first aquaporin, ‘aquaporin-1’ (originally known as CHIP 28), was reported by Peter Agre, of Johns Hopkins University.

The pioneering discoveries and research on water channels by Agre and his colleagues resulted in the presentation of a Nobel Prize in Chemistry to Agre in 2003. In 1999, together with other research teams, Agre reported the first high-resolution images of the three-dimensional structure of an aquaporin, namely, aquaporin-1. Further studies using supercomputer simulations have identified the pathway of water as it moves through the channel and demonstrated how a pore can allow water to pass without the passage of small solutes. However the first report of protein mediated water transport through membranes was by Gheorghe Benga in 1986. This publication that preceded Agre's first publication on water membrane transport proteins has led to a controversy that Benga's work was adequately recognized by neither Agre nor the Nobel Prize Committee. There is a long history of water pores, starting in 1957. There have been many reviews of the history.