Protein and Signaling Networks in Vertebrate Photoreceptor Cells

Abstract

Vertebrate photoreceptor cells are exquisite light detectors operating under very dim and bright illumination. The photoexcitation and adaptation machinery in photoreceptor cells consists of protein complexes that can form highly ordered supramolecular structures and control the homeostasis and mutual dependence of the secondary messengers cyclic guanosine monophosphate (cGMP) and Ca2+. The visual pigment in rod photoreceptors, the G protein-coupled receptor rhodopsin is organized in tracks of dimers thereby providing a signaling platform for the dynamic scaffolding of the G protein transducin. Illuminated rhodopsin is turned off by phosphorylation catalyzed by rhodopsin kinase (GRK1) under control of Ca2+-recoverin. The GRK1 protein complex partly assembles in lipid raft structures, where shutting off rhodopsin seems to be more effective. Re-synthesis of cGMP is another crucial step in the recovery of the photoresponse after illumination. It is catalyzed by membrane bound sensory guanylate cyclases (GCs) and is regulated by specific neuronal Ca2+-sensor proteins called guanylate cyclase-activating proteins (GCAPs). At least one GC (ROS-GC1) was shown to be part of a multiprotein complex having strong interactions with the cytoskeleton and being controlled in a multimodal Ca2+-dependent fashion. The final target of the cGMP signaling cascade is a cyclic nucleotide-gated (CNG) channel that is a hetero-oligomeric protein located in the plasma membrane and interacting with accessory proteins in highly organized microdomains. We summarize results and interpretations of findings related to the inhomogeneous organization of signaling units in photoreceptor outer segments.

Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

“…While currently unsupported by experimental evidence, we speculate that phosphorylation at these sites could have a function in modulating/ deactivating the photo-transduction cascade. This could proceed in a manner similar to the deactivation of rhodopsin, which after photoexcitation undergoes conformational changes that allow its phosphorylation by rhodopsin kinase [85]. It is then capped by arrestin thereby preventing further activation of transducine.…”

Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

“…While currently unsupported by experimental evidence, we speculate that phosphorylation at these sites could have a function in modulating/deactivating the photo-transduction cascade. This could proceed in a manner similar to the deactivation of rhodopsin, which after photoexcitation undergoes conformational changes that allow its phosphorylation by rhodopsin kinase [75]. It is then capped by arrestin thereby preventing further activation of transducine.…”

PRPH2/RDS and ROM-1: Historical context, current views and future considerations

“…Their synapses are in the outer plexiform layer, their nuclei are in the outer nuclear layer, their cell bodies with most of the mitochondria, endosomes, and protein synthesis machinery are in the inner segment layer, and finally their sensory OSs extend toward the RPE from the inner segments (Hoon et al, 2014; LaVail, 1983; Mustafi et al, 2009; Steinberg et al, 1980; Sung and Chuang, 2010). The photoreceptor OSs are modified primary cilia which have evolved to detect incoming light and initiate a signal transduction cascade which is the first domino in the long chain of signaling and cellular communications necessary for vision (Arshavsky and Wensel, 2013; Gilliam et al, 2012; Hoon et al, 2014; Hubbell et al, 2003; Koch and Dell’Orco, 2015; Li et al, 2004; Palczewski et al, 2000; Papermaster and Dreyer, 1974; Sung and Chuang, 2010; Zhou et al, 2012). …”