[Unknown mechanisms of the GPCR-signaling cascade in vertebrate photoreceptors].
Among the GPCR-signaling cascades, phototransduction in vertebrate retinal photoreceptors has been characterized in unprecedented details. It is believed that basic mechanisms of phototransduction and adaptation are reliably and completely established, and phototransduction may serve as a benchmark for understanding other G-protein-coupled systems. In this review, we compare present scheme of phototransduction with other GPCR-cascades in order to reveal their similarities and specific features. We show, based mainly on our physiological and biophysical data, that the existing scheme misses a few important regulations whose molecular basis is unknown. There exists a fast and efficient mechanism that accelerates the turn-off of the activated G-protein (transducin) during light adaptation. A few slowly acting processes result in a long-lasting modification of the cascade's components and regulate the speed of rhodopsin and transducin quenching. Similarly to other GPCR-cascades, one may suggest that there are multiple signalling pathways that start from photoactivated rhodopsin and rely on different secondary messengers (e.g. cAMP vs. cGMP). We also show that rhodopsin in retinal rods may form areas of paracristalline organization, and that the oligomerization might be a mechanism for controlling the amplification of the signalling cascade. The missing mechanisms are by no means minor, and could ensure sensitivity regulation within two orders of magnitude range.
V I
VI
Govardskiĭ
M L
ML
Firsov
D000221:Adaptation, Ocular / Q000502:physiology; D000818:Animals; D006801:Humans; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D043562:Receptors, G-Protein-Coupled