Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors.

The assembly of signalling molecules into macromolecular complexes (transducisomes) provides specificity, sensitivity and speed in intracellular signalling pathways. Rod photoreceptors in the eye contain an unusual set of glutamic-acid-rich proteins of unknown function. exist as two soluble forms, and and as a large cytoplasmic domain part) of the beta-subunit of the cyclic GMP-gated channel. Here we identify Gduanyu37s as multivalent proteins that interact with the key players of cGMP signalling, phosphodiesterase and guanylate cyclase, and with a retina-specific ATP-binding cassette transporter (ABCR), through four, short, repetitive sequences. In electron micrographs, Gduanyu37s are restricted to the rim region and incisures of discs in close proximity to the guanylate cyclase and ABCR, whereas the phosphodiesterase is randomly distributed. Gduanyu372, the most abundant splice form, associates more strongly with light-activated than with inactive phosphodiesterase, and potently inhibits phosphodiesterase activity. Thus, the Gduanyu37s organize a dynamic protein complex near the disc rim that may control cGMP turnover and possibly other light-dependent processes. Because there are no similar Gduanyu37s in cones, we propose that Gduanyu37s may prevent unnecessary cGMP turnover during daylight, when rods are held in saturation by the relatively high light levels.

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