title: The water permeability of lens aquaporin-0 depends on its lipid bilayer environment.
abstract: Aquaporin-0 (AQP0), the primary water channel in lens fiber cells, is critical to lens development, organization, and function. In the avascular lens there is thought to be an internal microcirculation associated with fluid movement. Although AQP0 is known to be important in fluid fluxes across membranes, the water permeability of this channel has only been measured in Xenopus oocytes and in outer lens cortical membranes, but not in inner nuclear membranes, which have an increased cholesterol/phospholipid ratio. Here we measure the unit water permeability of AQP0 in different proteoliposomes with cholesterol/phospholipid ratios and external pHs similar to those found in the cortex and nucleus of the lens. Osmotic stress measurements were performed with proteoliposomes containing AQP0 and three different lipids mixtures: (1) phosphatidylcholine (PC) and phosphatidylglycerol (PG), (2) PC, PG, with 40 mol% cholesterol, and (3) sphingomyelin (SM), PG, with 40 mol% cholesterol. At pH 7.5 the unit permeabilities of AQP0 were 3.5 ± 0.5 × 10(-14) cm(3)/s (mean ± SEM), 1.1 ± 0.1 × 10(-14) cm(3)/s, and 0.50 ± 0.04 × 10(-14) cm(3)/s in PC:PG, PC:PG:cholesterol, and SM:PG:cholesterol, respectively. For lipid mixtures at pH 6.5, corresponding to conditions found in the lens nucleus, the AQP0 permeabilities were 1.5 ± 0.4 × 10(-14) cm(3)/s and 0.76 ± 0.03 × 10(-14) cm(3)/s in PC:PG:cholesterol and SM:PG:cholesterol, respectively. Thus, although AQP0 unit permeability can be modified by changes in pH, it is also sensitive to changes in bilayer lipid composition, and decreases with increasing cholesterol and SM content. These data imply that AQP0 water permeability is regulated by bilayer lipid composition, so that AQP0 permeability would be significantly less in the lens nucleus than in the lens cortex.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jihong
authors.initials: J
authors.lastname: Tong
authors.forename: John T
authors.initials: JT
authors.lastname: Canty
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Briggs
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D002417:Cattle; D002463:Cell Membrane Permeability; D002784:Cholesterol / Q000737:chemistry; D005136:Eye Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007908:Lens, Crystalline / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D009995:Osmosis; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism*; D013109:Sphingomyelins / Q000737:chemistry; D014867:Water / Q000378:metabolism*
chemical_list: D020346:Aquaporins; D005136:Eye Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011510:Proteolipids; D013109:Sphingomyelins; C030328:aquaporin 0; C020485:proteoliposomes; D014867:Water; D002784:Cholesterol
keywords: aquaporin; cholesterol; fiber cells; lens; sphingomyelin; water permeability