Peter Agre – Lindau Nobel Laureate Meeting 2011

Aquaporin Water Channels: From Atomic Structure to Malaria

Abstract

The aquaporin water channel proteins confer high water permeability to biological membranes. Discovered in human red cells, AQP1 has been thoroughly characterized biophysically, and the atomic structure of AQP1 has been elucidated. Twelve homologous proteins have been identified in humans. These are selectively permeated by water (aquaporins) or water plus glycerol (aquaglyceroporins). The sites of expression predict the clinical phenotypes. Individuals lacking Colton blood group antigens have mutations in the AQP1 gene. When deprived of water, AQP1-null individuals exhibit a defect in urine concentration and a marked reduction in fluid exchange from lung capillaries. AQP1 is expressed in multiple tissues where physiologically important fluid secretion is known to occur including cerebrospinal fluid in brain and aqueous humor in eye. AQP2 is expressed in renal collecting duct principal cells where membrane trafficking is regulated by vasopressin. Mutations in the human AQP2 gene result in nephrogenic diabetes insipidus, but too little AQP2 expression is found in clinical disorders of urinary concentration, such as lithium therapy and bed wetting. Too much AQP2 expression is found in disorders of fluid retention, such as congestive heart failure and pregnancy. AQP0 is expressed in lens fiber cells and mutations result in familial cataracts. AQP5 is expressed in the apical membranes of salivary and lacrimal glands and sweat glands, and mistargetting may occur in some patients with Sjogren’s syndrome. Aquaporins have been implicated in other human clinical disorders such as brain edema, epilepsy, neuromyelitis optica (AQP4), anhidrosis (AQP5) renal tubular acidosis (AQP6). Aquaglyceroporins have been implicated in malaria, skin hydration (AQP3), glucose homeostasis during starvation and protection against arsenic poisoning (AQP7 and AQP9). Aquaporins are known to protect micro-organisms from freezing and osmotic shock. Plant aquaporins are involved in numerous processes including the uptake of water by rootlets and carbon dioxide by leaves. The physiological roles of aquaporin homologs are being pursued by multiple laboratories worldwide.

Beatrice Lugger

About Beatrice Lugger

Beatrice Lugger is a science journalist and science social media specialist with a background as a chemist. She is Deputy Scientific Director of the National Institute for Science Communication, NaWik – nawik.de – and a consultant for this blog. @BLugger is her twitter handle, Quantensprung her own blog.

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One comment on “Peter Agre – Lindau Nobel Laureate Meeting 2011

  • Heute ist Welt-Malaria-Tag (jährlich am 25.04.) und die Summe der Infizierten in aller Welt ist auch jetzt noch kritisch gross. Augenblicklich steht kein wirklich wirksamer Impfstoff zur Verfügung. Hier wird schon jahrelang geforscht. Mit der Einführung eines wirklich effektiven Impfstoffes wird momentan nicht vor 2019 gerechnet.

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