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. 2021 Feb 2;296:100362. doi: 10.1016/j.jbc.2021.100362

Figure 1.

Figure 1

Two hypothetical roles of RD3 in preventing photoreceptor degeneration.A, Hypothesis 1: RD3 is required to suppress aberrant activation of RetGC cyclase by GCAPs (17, 18, 19). In normal photoreceptors, the membrane guanylyl cyclase (RetGC) is delivered with the help of RD3 to the outer segment, where it produces cGMP for phototransduction. While in the inner segment, the RetGC is suppressed by RD3 blocking the cyclase activation by GCAPs. In RD3-deficient photoreceptors, RetGC content in the outer segment is strongly reduced, but the cyclase remaining in the inner segment becomes unprotected against activation by GCAPs, and this triggers the apoptotic process. B, Hypothesis 2: RD3 accelerates GMP phosphorylation by guanylate kinase (20). In the light, RetGC rapidly converts GTP to cGMP, and then PDE6 converts cGMP to 5’GMP. RD3 stimulates guanylate kinase activity to convert GMP to GDP and then back to GTP. The RD3-deficient photoreceptors fail to phosphorylate GMP; therefore, the RetGC/PDE6 pathway depletes the GDP/GTP pool and thus causes photoreceptor degeneration (20). GCAP, guanylyl cyclase activating protein; RD3, retinal degeneration 3 protein; RetGC, retinal membrane guanylyl cyclase; PDE6, cGMP phosphodiesterase 6.