Abstract
Retinal degeneration protein 3 (RD3) is crucial for photoreceptor cell survival and linked to Leber Congenital Amaurosis type 12 (LCA12), a hereditary retinal disease in humans. RD3 inhibits photoreceptor guanylate cyclases GC-E and GC-F and is involved in transport of GCs from the inner to the outer segments. Otherwise, its role in photoreceptor physiology is poorly understood. Here, we describe a new function of RD3. Purified RD3 evoked an increase in guanylate kinase activity, an enzyme that is involved in the nucleotide cycle in photoreceptors. We demonstrate a direct interaction between guanylate kinase and RD3 using back-scattering interferometry and show by immunohistochemistry of mouse retina sections that RD3 and guanylate kinase co-localize in photoreceptor inner segments and to a lesser extent in the outer plexiform layer. Our findings point toward a more complex function of RD3 in photoreceptors. The RD3 – guanylate kinase interaction may also play a role in other cellular systems, while the GC – RD3 interaction is exclusive to photoreceptors.
Highlights
Retinal dystrophies are heterogeneous disorders that typically result in the degeneration of photoreceptors leading to severe impairment or loss of vision
This study started by testing the role of Retinal degeneration protein 3 (RD3) interacting with GC-E (Azadi et al, 2010; Peshenko et al, 2011)
Within 4 h after the induction of protein expression in E. coli, a high amount of RD3 is produced becoming visible as an intense band around 26 kDa in a polyacrylamide gel
Summary
Retinal dystrophies are heterogeneous disorders that typically result in the degeneration of photoreceptors leading to severe impairment or loss of vision. Different retinal disease forms include retinitis pigmentosa (RP), cone-rod or cone dystrophies (CORD/COD), Leber congenital amaurosis (LCA), color vision defects, night blindness and others (for a comprehensive review see Berger et al, 2010) Among these hereditary diseases, LCA is a severe form of retinal degeneration causing blindness after birth or in the 1st year of life. Excitation and adaptation of rod and cone cells is characterized by a fine-balanced homeostasis and interplay of 2 second messengers, cytoplasmic cGMP and Ca2+ (Koch and Dell’Orco, 2015) This cGMP signaling system is further impaired by mutations in GUCA1A coding for the Ca2+-sensor protein GCAP1, which is an essential regulator of GC-E activity (Palczewski et al, 1994; Frins et al, 1996; Olshevskaya et al, 2012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
