Knock-Out Models Reveal New Aquaporin Functions
Knockout mice have been informative in the discovery of unexpected biological functions of aquaporins. Knockout mice have confirmed the predicted roles of aquaporins in transepithelial fluid transport, as in the urinary concentrating mechanism and glandul
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AQPs and the Urinary Concentrating Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AQPs in Active, Near-Isosmolar Fluid Secretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AQP4 in Brain Swelling and Neural Signal Transduction . . . . . . . . . . . . . . . . . . . . . . . . . . . AQPs and Eye Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AQPs in Angiogenesis and Cell Migration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physiological Roles for Glycerol Transport by Aquaglyceroporins . . . . . . . . . . . . . . . . . . . 7.1 AQP3 and Skin Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 AQP3 and Cell Proliferation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3 AQP7 and Fat Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Summary and Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Knockout mice have been informative in the discovery of unexpected biological functions of aquaporins. Knockout mice have confirmed the predicted roles of aquaporins in transepithelial fluid transport, as in the urinary concentrating mechanism and glandular fluid secretion. A less obvious, though predictable role of aquaporins is in tissue swelling under stress, as in the brain in stroke, tumor and infection. Phenotype analysis of aquaporin knockout mice has revealed several unexpected cellular roles of aquaporins whose mechanisms are being elucidated. Aquaporins facilitate cell migration, as seen in aquaporin-dependent tumor angiogenesis and tumor metastasis, by a mechanism that may involve facilitated water transport in lamellipodia of migrating cells. The ‘aquaglyceroporins’, aquaporins that transport both glycerol and water, regulate glycerol content in epidermis, fat and other tissues, and lead to a multiplicity of interesting consequences of gene disruption including dry skin, resistance to skin carcinogenesis, impaired cell A.S. Verkman Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA, 94143-0521, USA [email protected] E. Beitz (ed.), Aquaporins, Handbook of Experimental Pharmacology 190, c Springer-Verlag Berlin Heidelberg 2009
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proliferation and altered fat metabolism. An even more surprising role of a mammalian aquaporin is in neural signal transduction in the central nervous system.
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