Patients who suffer form inherited retinal degenerations carry very often mutations in genes that code for proteins involved in rod or cone signal transduction. So far our group has investigated the biochemical consequences of mutations of the photoreceptor specific guanylate cyclase ROS-GC1 (GC-E), which were found in patients suffering from Leber´s congenital amaurosis and cone-rod-dystrophies. We plan to extend these investigations to mutations found in the opsin gene of retinitis pigmentosa patients. So far over 150 different mutations in the opsin gene were detected, but in most cases the biochemical and cellular consequences leading to cell degeneration are unknown. We will investigate, whether protein-protein interactions are disturbed in the signalling chain consisting of rhodopsin, G-protein transducin, rhodopsin kinase and arrestin. For this purpose we immobilize rhodopsin or mutants of rhodopsin on biosensor chip surfaces and study the interactions with binding partners by surface plasmon resonance spectroscopy.

Kitiratschky, V. B. D., Behnen, P., Kellner, U., Heckenlively, J. R., Zrenner, E., Jägle, H., Kohl, S., Wissinger, B. and Koch, K.-W. (2009) Mutations in the GUCA1A gene involved in hereditary cone dystrophies impair calcium-mediated regulation of guanlyate cyclase. Hum. Mutat. 30, E782-796

Dell'Orco, D., Behnen P., Linse, S. and Koch, K.-W. (2010) Calcium binding, structural stability and guanylate cyclase activation in GCAP1 variants associated with human cone dystrophy. Cell. Mol. Life. Sci. Mar; 67(6):973-84

Dell'Orco, D., Sulmann, S., Zägel, P., Marino, V. and Koch, K.-W. (2014) Impact of cone dystrophy-related mutations in GCAP1 on a kinetic model of phototransduction. Cell. Mol. Life Sci. 71, 3829-3840.

Marino, V., Scholten, A., Koch, K.-W. and Dell'Orco, D. (2015) Two retinal dystrophy-associated missense mutations in GUCA1A with distinct molecular properties result in a similar aberrant regulation of the retinal guanylate cyclase. Hum. Mol. Genet. 24, 6653-6666.

Vocke, F., Weisschuh, N., Marino, V., Malfatti, S., Jacobson, S.G., Reiff, C. M., Dell’Orco, D., and Koch, K.-W. (2017) Dysfunction of cGMP signaling in photoreceptors by a Macular Dystrophy-related mutation in the calcium sensor GCAP1. Hum. Mol. Genet. 26, 133-144.

Wimberg, H., Lev, D., Yosovich, K., Namburi, P., Banin, E., Sharon, D. and Koch, K.-W. (2018) Photoreceptor Guanylate Cyclase (GUCY2D) mutations cause retinal dystrophies by severe malfunction of Ca²⁺-dependent cyclic GMP synthesis. Front. Mol. Neurosci. Vol. 11:348. doi: 10.3389/fnmol.2018.00348.

Sharon, D., Wimberg, H., Kinarty, Y. and Koch, K.-W. (2018) Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D. Prog. Retin. Eye Res. 63, 69-91.

Avesani, A., Bielefeld, L., Weisschuh, N., Marino, V., Mazzola, P., Stingl, K., Haack, T.B., Koch, K.W., and Dell'Orco, D. (2022) Molecular Properties of Human Guanylate Cyclase-Activating Protein 3 (GCAP3) and Its Possible Association with Retinitis Pigmentosa. Int. J. Mol. Sci. 23(6):3240.