ras-p21 Proteins: Switch Devices for Signal Transduction
Juan Carlos Lacal, Frank McCormick in The ras Superfamily of GTPases, 2017
Gs, Gi, transducin, and Gq belong to a large family of proteins involved in receptor-induced signal transduction processes. They function as heterotrimeric complexes (α,β,γ) where only their α-subunits are able to bind guanine nucleotides with high efficiency.60-64 These classical, heterotrimeric G proteins respond to activated receptors by liberating their α-subunits from the complex at the same time that bound GDP is replaced by GTP (see Figure 1). The activated, GTP-bound α-subunits acquire an active state which allows them to interact with their effector molecules. All known G proteins return to the inactive state by virtue of their intrinsic GTPase activity which converts GTP to GDP. As indicated above, amino acid sequence comparison ofras-p21 with that of α-chains of GTP-binding proteins, such as Gs and Gi, revealed a consistent pattern of homology, especially in regions of the molecule involved in their GTP-binding and GTPase properties.65-66
Guanosine Triphosphate-Binding Proteins
Enrique Pimentel in Handbook of Growth Factors, 2017
Transductional mechanisms involving GTP-binding proteins depend on the interaction of three essential components on the cell surface: a receptor, a GTP-binding protein, and an effector. In hormonally regulated systems the signal is the hormone, which is recognized by its specific receptor, and the GTP-binding component is a trimeric (α,β,γ) G protein. In the visual system, the exogenous signals are represented by photons, which are captured in the retina by the specific receptor, rhodopsin, and the GTP-binding protein is called transducin.12,13 The GTP-binding proteins are thus involved in mediating the transduction of both physical and chemical signals across the cell membrane. A growing number of low molecular weight GTP-binding proteins (G proteins) have been identified in eukaryotic cells. G proteins are structurally and functionally related to the 21-kDa (p21) Ras protein products of c-ras proto-oncogenes.
Comparative Anatomy and Physiology of the Mammalian Eye
David W. Hobson in Dermal and Ocular Toxicology, 2020
There is a steady dark current that flows along the length of the photoreceptors. This current is maintained by Na+ which is extruded from the inner segment by a Na+-K+-ATPase pump and then enters passively through Na+ channels in the outer segment.129,135 Thus, during darkness, the photoreceptors are continuously discharging. Exposure to light results in the closure of the Na+ channels in the outer segment and a resultant hyperpolarization and a decrease in the release of neurotransmitter. This process is termed transduction and involves the absorption of a photon by rhodopsin. This, in turn, communicates via a molecule termed transducin to activate the enzyme phosphodiesterase which will hydrolyze many cyclic GMP molecules which are responsible for maintaining the Na+ channels.129 It is this phosphodiesterase enzyme that has been found to be abnormal in animals, such as the Irish Setter and Collie dogs and the Rd mouse, that undergo hereditary retinal degeneration. The signal from the photoreceptor cell is transmitted inwards to the ganglion cells via the bipolar cell with input from the horizontal and amacrine cell. The neurotransmitters involved in this process may include GABA, glycine, acetylcholine, monoamines, peptides, substance-P, aspartate, and glutamate.136,137
Novel homozygous in-frame deletion of GNAT1 gene causes golden appearance of fundus and reduced scotopic ERGs similar to that in Oguchi disease in Japanese family
Published in Ophthalmic Genetics, 2019
Daiki Kubota, Noriko Oishi, Kiyoko Gocho, Sachiko Kikuchi, Kunihiko Yamaki, Tsutomu Igarashi, Hiroshi Takahashi, Nobuo Ishida, Takeshi Iwata, Atsushi Mizota, Shuhei Kameya
The GNAT1 gene (OMIM *139330) encodes α subunit of rod transducin, a protein naturally expressed in vertebrate. Transducin is an important part of the phototransduction cascade (1,2) and is a trimeric G protein that consists of three subunits (3). The alpha-subunit binds to guanosine triphosphate (GTP) and activates cyclic guanosine monophosphate-phosphodiesterase (cGMP-PDE). The beta and gamma subunits form a complex that makes it possible for transducin to interact with rhodopsin (4). On exposure of the photoreceptor cells to light, rhodopsin is photoisomerized to its active form. This form activates transducin which then stimulates cGMP-PDE. The degradation of cGMP cause cGMP-gated ion channels to close resulting in hyperpolarization of the photoreceptors causing the electrical light response (5). The alpha-subunit is encoded by GNAT1 and is expressed in the rod cells, whereas the alpha-subunit that is encoded by GNAT2 is expressed in the cone cells (1,6).
Achromatopsia: clinical features, molecular genetics, animal models and therapeutic options
Published in Ophthalmic Genetics, 2018
Nashila Hirji, Jonathan Aboshiha, Michalis Georgiou, James Bainbridge, Michel Michaelides
GNAT2 was the third gene found to be associated with ACHM, and accounts for less than 2% of all cases (42). GNAT2 mutations have been found in cases of both complete and incomplete ACHM (23,52). The variant c.461 + 24G>A which results in abnormal splicing in vitro is thought to result in an incomplete ACHM phenotype (52). Other mutations in this gene have been found to produce a truncated non-functional transducin protein (53). PDE6C mutations also account for less than 2% of ACHM cases, and in vitro studies have demonstrated that missense mutations result in enzymatic dysfunction, ranging from reduced to complete loss of activity (54). PDE6H mutations are the rarest cause of ACHM, accounting for less than 1% of affected individuals. The most recent gene, ATF6, accounts for 1–2% of ACHM with sequence variants found to cause both complete and incomplete ACHM (40).
Non-paraneoplastic related retinopathy: clinical challenges and review
Published in Ophthalmic Genetics, 2019
Júlia T. Takiuti, Vitor K. L. Takahashi, Christine L. Xu, Ruben Jauregui, Stephen H. Tsang
Transducin, also known as G-protein, is a 3-subunit guanine nucleotide-binding protein that stimulates the coupling of cGMP-phosphodiesterase to cGMP in the photo-transduction cascade leading to hyperpolarization of the photoreceptor. Transducins have three protein subunits, α, β, and γ. In rods and cones, the transducin α -subunits are encoded by separate genes: GNAT1 in rods and GNAT2 in cones (20). When transducin-α is inactivated by autoantibodies, there may be a reduction in photoreceptor signaling as well as changes in apoptosis and intracellular calcium levels. (31)
Related Knowledge Centers
- Absorption
- Cyclic Guanosine Monophosphate
- Gene Expression
- Heterotrimeric G Protein
- Phosphodiesterase
- Protein
- Retina
- Retinal
- Rhodopsin
- Visual Phototransduction