Gap junction communication influences intercellular protein distribution in the lens

Lens transparency and high refractive index presumably depend on the appropriate arrangement and distribution of lens proteins among lens fiber cells. Intercellular gap junction channels formed by alpha 3 and,alpha 8 connexins are known to transport small molecules, ions and water, but not proteins, in the lens. Mosaic expression of green fluorescent protein (GFP) in the lens is a useful marker for monitoring macromolecule distribution between fiber cells and for constructing three-dimensional images of living lens cells. In alpha 3(-/-) alpha 8(-/-) double knockout (DKO) tenses, three-dimensional images of GFP-positive cells demonstrate the changes of epithelial cell surfaces and insufficient elongation of inner fiber cells. Uniform distribution of GFP between inner lens fiber cells is observed in both wild-type and alpha 3(-/-) lenses. In contrast, uniform GFP distribution is slightly delayed in alpha 8(-/-) lenses and is abolished in DKO lenses. Without endogenous wild-type alpha 3 and alpha 8 connexins, knock-in alpha 3 connexin (expressed under the alpha 8 gene promoter) restores the uniform distribution of GFP protein in the lens. Thus, the presence of either alpha 3 or alpha 8 connexins seems sufficient to support the uniform distribution of GFP between differentiated lens fiber cells. Although the mechanism that drives GFP transport between fiber cells remains unknown, this work reveals that gap junction communication plays a novel role in the regulation of intercellular protein distribution in the lens. Published by Elsevier Ltd.