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First published online August 3, 2005
doi: 10.1242/10.1242/jcs.02519


Journal of Cell Science 118, 3225-3232 (2005)
Published by The Company of Biologists 2005
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More than just water channels: unexpected cellular roles of aquaporins

A. S. Verkman

Departments of Medicine and Physiology, Cardiovascular Research Institute, Room 1246, Box 0521 University of California San Francisco, San Francisco, CA 94143-0521, USA



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Fig. 1. Structure of AQP1 monomers and their tetrameric assembly in membranes. (A) Crystal structure of AQP1 monomer showing tilted transmembrane {alpha}-helical domains (numbered 1-6) surrounding a water pore. Conserved `NPA' motifs are indicated. (B) Tetrameric assembly of AQP1 in a membrane in which individual monomers contain water pores.

 


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Fig. 2. Involvement of AQPs in epithelial fluid transport. (A) Reduced trans-epithelial water permeability in the kidney collecting duct impairs urinary concentrating ability by preventing osmotic equilibration of luminal fluid. (B) Reduced water permeability in glandular epithelium impairs active, near-isosmolar fluid transport by slowing osmotic water transport into the acinar lumen, producing hypertonic secretion.

 


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Fig. 3. Involvement of AQP4 in brain swelling. Pathways for water entry into and exit from brain, showing AQP4-dependent water movement across the blood-brain barrier, and through ependymal and arachnoid barriers.

 


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Fig. 4. AQP1 in migrating cells. (A) AQP1 (green, white arrows) localizes to lamellipodia in migrating AQP1-expressing CHO cells. Actin is stained red. (B) Proposed mechanism of AQP-dependent cell migration, showing water influx at the tip of a lamellipodium resulting in membrane protrusion.

 


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Fig. 5. Reduced skin hydration in AQP3 deficiency. (A) Schematic showing stratum corneum and epidermal layers. (B) Immunofluorescence showing AQP3 (in yellow) in the basal layer of epidermal cells in mice. E, epidermis; D, dermis; sc, stratum corneum. (C) Proposed mechanism of AQP3 function in skin, showing reduced steady-state glycerol content in epidermis and stratum corneum following AQP3 deletion.

 


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Fig. 6. Progressive fat accumulation and adipocyte hypertrophy in AQP7 deficiency. (A) Histology of gonadal white adipose tissue in AQP7-null mice at age 16 weeks, showing marked adipocyte hypertrophy. (B) Proposed mechanism for adipocyte hypertrophy in AQP7 deficiency, in which impaired AQP7-dependent glycerol escape results in intracellular glycerol accumulation and increased triglyceride (TG) content. FFA, free fatty acid.

 


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Fig. 7. Possible mechanisms for involvement of AQPs in rapid neural signal transduction. AQP4 expression on astroglia may alter the volume of the extracellular space and its composition by interactions with Kir4.1 K+ channels or by impairing water re-uptake into astroglia during neural signaling.

 





© The Company of Biologists Ltd 2005