Phototransduction protein

Mutations in phototransduction proteins are a major cause of retinitis pigmentosa and other photoreceptor degenerations... 

Photoreceptors continually synthesize new phototransduction proteins for incorporation into newly formed outer segment discs. As new discs are formed at the base of the outer segment, older discs are phagocytosed by RPE cells at the tip of the outer segment. Each outer segment disc is formed and shed in 2 weeks. The phagocytosis of discs occurs in circadian bursts (rods at the end of night, cones at the end of day). 

This family contains more than 40 members subdivided into five subfamilies [4]. The NCS have been involved in phototransduction and regulation of neurotransmitter release. The NCS have two pairs of EF-hands and, unlike CaM and SI00 proteins, possess a consensus myristoylation sequence at the N-terminal responsible for the targeting of the NCS to the membrane. 

A second class of neuronal calcium sensors is formed by the guanylate cyclase-activating protein (GCAP). The GCAPs are expressed only in the photoreceptor cells of the retina of vertebrates. Recoverins and GCAPs have antagonistic roles in phototransduction. 

A key feature of both vertebrate and invertebrate opsin molecules is their ability to interact with a G protein, typically transducin, to initiate phototransduction (Ebrey Koutalos 2001). The third cytoplasmic loop that connects a-hehces V and VI contributes to the G protein binding and activation and is highly conserved amongst the rod and cone opsins (Fig. 1, Table 2). This conservation extends to the P opsin family. However, the third cytoplasmic loop of the VA... 

Lamb, T.D. Gain and kinetics of activation in the G-protein cascade of phototransduction (1996) Proc. Natl. Acad. Sd. U.S.A. 93, 566-570... 

Montell, C. and Rubin, G.M. Molecular characterization of the Drosophila trp locus a putative integral membrane protein required for phototransduction, Neuron 1989, 2,1313-1323. 

The three-dimensional structures of the reaction centers of purple bacteria (Rhodopseudomonas viridis and Rhodobacter sphaeroides), deduced from x-ray crystallography, shed light on how phototransduction takes place in a pheophytin-quinone reaction center. The R. viridis reaction center (Fig. 19-48a) is a large protein complex containing four polypeptide subunits and 13 cofactors two pairs of bacterial chlorophylls, a pair of pheophytins, two quinones, a nonheme iron, and four hemes in the associated c-type cytochrome. 

Our work aims at identifying, by subpicosecond broadband transient absorption and gain spectroscopy, the primary photochemical steps of the phototransduction process in Blepharisma japonicum, more specifically in the light-adapted form of the organism (blue cell) for which the photoactive pigment is oxyblepharismin [5] (see Scheme 1) and the associated macromolecule is a large non-soluble protein (200 kDa) [6]. 

The dynamic behavior of the chromoprotein is much more clearly multiexponential. Two pronounced decay components were identified with 5-ps (25 % wt.) and 60-ps (25% wt.) lifetimes. The strong weight of these exponentials is not in favor of a comparison to the weak 13-ps decay of the free pigment. It is more likely that they actually reveal a new and specific deactivation channel in the protein complex. It has, in fact, been speculated that light irradiation of the living organism induces an acidification of the intracellular medium [11], so proton transfer from the chromophore to the associated protein was first proposed as the initial phototransduction step. More recent experiments on the isolated pigment in the presence of electron acceptors [12] proved that the optical excitation can induce an electron transfer from the chromophore to an acceptor site possibly situated inside the associated... 

Figure 2. The rod phototransduction cascade and human diseases associated with mutations in GC1 and GCAP1. The main proteins of the cascade are shown in gray. GC1 and GCAP1 represent the main components of the Ca2+-regulated GC in rods and cones responsible for cGMP synthesis. IPM = Interphotoreceptor Matrix (See Colour Plate 7)...

Vanadate(V) and GTP-y-S, a hydrolysis resistant analog of GTP, have recently been shown to excite photoreceptors of the horseshoe crab Limulus in the dark and have been used to help elucidate the chemical steps which are involved in the phototransduction process153. The results suggest that vanadate binds to a guanyl nucleotide binding protein which activates adenylate cyclase. 

---