Mechanism of light‐induced translocation of arrestin and transducin in photoreceptors: Interaction‐restricted diffusion

Abstract

SummaryMany signaling proteins change their location within cells in response to external stimuli. In photoreceptors, this phenomenon is remarkably robust. The G protein of rod photoreceptors and rod transducin concentrates in the outer segments (OS) of these neurons in darkness. Within 30 minutes after illumination, rod transducin redistributes throughout all of the outer and inner compartments of the cell. Visual arrestin concurrently relocalises from the inner compartments to become sequestered primarily within the OS. In the past several years, the question of whether these proteins are actively moved by molecular motors or whether they are redistributed by simple diffusion has been extensively debated. This review focuses on the most essential works in the area and concludes that the basic principle driving this protein movement is diffusion. The directionality and light dependence of this movement is achieved by the interactions of arrestin and transducin with their spatially restricted binding partners.

Regulation of Arrestin Translocation by Ca2+ and Myosin III in Drosophila Photoreceptors

“…9) differs fundamentally from an earlier model in which NINAC was proposed as a molecular motor transporting Arr2 in phosphoinositide-rich vesicles (Lee and Montell, 2004). By contrast it shows strong parallels with current models for arrestin translocation in vertebrate rods (Calvert et al, 2006;Slepak and Hurley, 2008). Here, phosphorylated rhodopsin represents the light-activated sink in the outer segments, while microtubules have been proposed as the cytosolic sink in the inner segments (Nair et al, 2005).…”

“…The mechanism is unclear; however, intriguingly a recent study has implicated roles for PLC and protein kinase C possibly stimulating release of arrestin from its cytosolic sink (Orisme et al, 2010). Such regulated-sink models have the advantage of simplicity: directed translocation requires no more than diffusion coupled with regulated binding, can rapidly transport virtually unlimited quantities of protein, and per se consumes essentially no energy (Nair et al, 2005;Slepak and Hurley, 2008) (but see Orisme et al, 2010). While it can be conveniently studied in photoreceptors with their distinctive polarized morphologies and high concentrations of transduction machinery, translocation according to the same general principles may represent a general and elegant solution to the problem of directed movements of signaling proteins.…”

“…It has recently become widely recognized that several phototransduction proteins translocate between these compartments in response to light, representing a form of long-term light and dark adaptation (for review, see Frechter and Minke, 2006;Slepak and Hurley, 2008). One of the best-studied examples is arrestin, which terminates the light response by binding to photo-isomerized rhodopsin (metarhodopsin).…”

“…One of the best-studied examples is arrestin, which terminates the light response by binding to photo-isomerized rhodopsin (metarhodopsin). In dark-adapted photoreceptors most arrestin localizes to the cell body in both vertebrate and insect photoreceptors, but on illumination translocates to the photosensory compartment (Broekhuyse et al, 1985;Alloway et al, 2000;Kiselev et al, 2000;Lee et al, 2003;Peterson et al, 2003;Calvert et al, 2006;Slepak and Hurley, 2008;Satoh et al, 2010). In fly (Drosophila) photoreceptors the photosensory compartment is represented by the rhabdomere, a lightguiding, rod-like stack of ϳ30,000 densely packed apical microvilli loaded with rhodopsin and proteins of a phototransduction cascade mediated by heterotrimeric Gq protein, phospholipase C (PLC), and Ca 2ϩ -permeable "transient receptor potential" (TRP) channels (for review, see Wang and Montell, 2007;Katz and Minke, 2009;Yau and Hardie, 2009;Hardie, 2012).…”

“…Although the possible role of active transport by molecular motors remains debated (Lee and Montell, 2004;Calvert et al, 2006;Strissel et al, 2006;Orisme et al, 2010), recent evidence in both vertebrate rods and Drosophila microvillar photoreceptors supports an essentially passive diffusional model of arrestin translocation, down gradients established by light-regulated "sinks" (Nair et al, 2005;Slepak and Hurley, 2008;Satoh et al, 2010). We recently provided evidence that metarhodopsin (M) is the major light-activated sink in fly rhabdomeres by showing that the dominant arrestin isoform (Arr2) translocated in a 1:1 stoichiometric relationship to the number of rhodopsin photoisomerizations (Satoh et al, 2010).…”