Unknown Mechanisms Regulating the GPCR Signal Cascade in Vertebrate Photoreceptors

Abstract

The process of phototransduction – the conversion of a light signal into an electrical response occurring in vertebrate photoreceptors – is the best studied and characterized example of a GPCR signal cascade. The literature contains the view that the basic mechanisms of phototransduction are already known and that data obtained from photoreceptors can be applied to other GPCR signaling systems. In this review, we compare the contemporary model of phototransduction with data from studies of other GPCR signal cascades with the aim of identifying similarities and differences between them. Working mainly from physiological and biophysical data, we show that the current scheme of phototransduction lacks important regulatory mechanisms, whose biochemical substrates remain unknown. This provides, for example, rapid control of the lifetime of the active state of G-protein (transducin) during light adaptation. There are also slow (several minutes) processes modifying components of the signal cascade which regulate the rate of deactivation of activated receptor (rhodopsin) and transducin. By analogy with other GPCR signal cascades, the existence of several other signaling pathways from light-activated rhodopsin can be suggested; these may use different second messengers (not only cGMP but also, for example, cAMP). We also show that rhodopsin oligomerization may occur in photoreceptors and that this process may provide physiological control of amplification in the signal cascade. The missing mechanisms are by no means unimportant and may support regulation of photoreceptor sensitivity over a range from one to two orders of magnitude.