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Exp Eye Res
2013 Aug 01;113:32-40. doi: 10.1016/j.exer.2013.04.022.
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The water permeability of lens aquaporin-0 depends on its lipid bilayer environment.
Tong J, Canty JT, Briggs MM, McIntosh TJ.
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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 lensnucleus, 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 lensnucleus than in the lens cortex.
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Fig. 1. Osmotic gradient-driven changes in light scattering for POPC:POPG:cholesterol bilayers without protein or in the presence of AQP0 at a protein/lipid molar ratio of 0.002. For both systems, the osmotic gradient was applied at t = 0 and the traces were graphed on the same relative scale by normalizing the light scattering to go from 0 at t = 0 to +1 when the scattering plateaued. Fits to the data (single-exponential in the absence of AQP0 and double-exponential in the presence of AQP0) are shown as dotted black lines. With and without AQP0 the fits to the data gave root mean square errors (RMSE) <0.005.
Fig. 2. Traces of osmotic gradient-driven changes in light scattering for proteoliposomes containing AQP0 at similar protein/lipid (P/L) molar ratios: POPC:POPG (P/L = 0.002) (red), POPC:POPG:cholesterol (P/L = 0.002) (blue), and SM:DPPG:cholesterol (P/L = 0.003) (green). The light scattering traces were normalized as in Fig. 1. Although data were recorded for a 20-s time period in order for the SM:DPPG:cholesterol trace to plateau, the light-scattering data are displayed for only the first five seconds to better show the differences among the three lipid systems. Double-exponential fits to the data are shown as dotted black lines with fits to all data sets in this paper giving RMSE <0.005.
Fig. 3. Plot of proteoliposome permeability (pf) as a function of molar protein/lipid (P/L) ratio for AQP0 in bilayers composed of POPC:POPG (red circles), POPC:POPG:cholesterol (blue squares), and SM:DPPG:cholesterol (green triangles). For each lipid composition fits to the osmotic gradient-driven traces (Fig. 2) yielded two shrinkage rates, with k1 giving values of pf that increased linearly with increasing values of P/L (solid symbols), and k2 giving values of pf that were nearly independent of P/L (open green triangles show these values for SM:DPPG:cholesterol).
Fig. 4. Single-channel (unit) permeabilities for AQP0 for bilayers composed of POPC:POPG, POPC:POPG:cholesterol, and SM:DPPG:cholesterol obtained at pH 7.5. (For simplicity, the lipid labels on the x-axis do not include the relevant PG.)
Fig. 5. Single-channel (unit) permeabilities for AQP0 and AQP4-M1 isoform in bilayers composed of POPC:POPG, POPC:POPG:cholesterol, and SM:DPPG:cholesterol at pH 7.5. The AQP4-M1 data are taken from Tong et al. (2012).
Fig. 6. Single-channel (unit) permeabilities for AQP0 in bilayers composed of POPC:POPG:cholesterol and SM:DPPG:cholesterol at pH 7.5 and at pH 6.5.
Fig. 7. Single-channel (unit) water permeabilities at pH 7.5 for AQP0 in bilayers composed of POPC:POPG, POPC:POPG:cholesterol, and SM:DPPG:cholesterol plotted as a function of (A) bilayer hydrocarbon thickness and (B) the square-root of bilayer area compressibility modulus
. Linear fits to the data are shown to guide the eye.
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