The role of MIP in lens fiber cell membrane transport

MTP has been hypothesized to be a gap junction protein, a membrane ion chan nel, a membrane water channel and a facilitator of glycerol transport and m etabolism. These possible roles have been indirectly suggested by the local ization of MIP in lens gap junctional plaques and the properties of MIP whe n reconstituted into artificial membranes or exogenously expressed in oocyt es. We have examined lens fiber cells to see if these functions are present and whether they are affected by a mutation of MIP found in Cat(Fr) mouse lens. Of these five hypothesized functions, only one, the role of water cha nnel, appears to be true of fiber cells in situ. Based on the rate of volum e change of vesicles placed in a hypertonic solution, fiber cell membrane l ipids have a low water permeability (p(H2O)) on the order of 1 mu m/sec whe reas normal fiber cell membrane p(H2O) was 17 mu m/sec frog, 32 mu m/sec ra bbit and 43 mu m/sec mouse. Cat(Fr) mouse lens fiber cell p(H2O) was reduce d by 13 mu m/sec for heterozygous and 30 mu m/sec for homozygous mutants wh en compared to wild type, Lastly, when expressed in oocytes, the p(H2O) con ferred by MIP is not sensitive to Hg2+ whereas that of CHIP28 (AQP1) is blo cked by Hg2+. The fiber cell membrane p(H2O) was also not sensitive to Hg2 whereas lens epithelial cell p(H2O) (136 mu m/sec in rabbit) was blocked b y Hg2+. With regard to the other hypothesized roles, fiber cell membrane or lipid vesicles had a glycerol permeability on the order of 1 nm/sec, an or der of magnitude less than that conferred by MIP when expressed in oocytes. Impedance studies were employed to determine gap junctional coupling and f iber cell membrane conductance in wild-type and heterozygous Cat(Fr) mouse lenses. There was no detectable difference in either coupling or conductanc e between the wild-type and the mutant lenses.