Two are better than one: unraveling the functions of cone arrestin in zebrafish (Commentary on Renninger, Gesemann and Neuhauss)

Since the surprising discovery of a second visual arrestin in mammalian pinealocytes and cone photoreceptors, numerous studies have examined cone arrestin's structural and functional similarities to and differences from rod arrestin (Craft et al., 1994; Nikonov et al., 2008). The rod arrestin or Arrestin1 binds to and terminates the light-activated, phosphorylated G-protein-coupled rhodopsin (Xu et al., 1997), whereas both visualarrestins work in concert in cone photoreceptors to shut off the light-activated photoreceptor signal transduction cascade, as shown for mouse Sand M-opsin (Nikonov et al., 2008).In this issue of EJN, Renninger and colleagues add a new dimension to understanding the visual arrestin saga by introducing two rod arrestins (arrS), three b-arrestins, and focusing on two paralogs of cone arrestin (arr3a and arr3b) in the zebrafish (Danio rerio). The Arr3a is exclusively expressed in M- and L-wavelength sensitive cones, whereas Arr3b is found in S- and UV-wavelength-sensitive cones. Their comprehensive study provides the first clear evidence of Arr3a's involvement in the high temporal contrast sensitivity of cone vision.As zebrafish exhibit light responses after 3 days of development, they are an ideal animal to study visual behavior (Brockerhoff et al., 1995). They are tetrachromatic with ultraviolet-sensitive cones as well as red-, green- and blue-sensitive cones, and their retinas continue to grow throughout their life. Using this cone-dominated visual system as a model system for their analysis, Renninger et al. (2011) examined the cellular expression of the distinct isoforms of arrestin in the visual system using a combination of in-situ hybridization and cone arrestin paralog-specific antibodies to examine cellular distribution at different developmental stages. These straightforward morphological experiments were followed by aset of elegant physiological experiments using targeted gene knockdown of the two cone arrestins in zebrafish larvae to unravel their visual responses with electroretinography. The functional knockdown of arr3a led to an electroretinography photo-response recovery delay. Additional experiments with the functional inactivation of arr3a were used to dissect out the psychophysical responses with optokinetics, a stereotypic ocular movement that is probably mediated by the modulation of M- and L-cone input (Orger & Baier, 2005). These latter experiments distinguished behavioral differences between low-contrast (dark-adapted) conditions that affected high temporal frequency patterns, and high-contrast (lightadapted)conditions that showed a deceleration of the temporal transfer function in the arr3a morphant larvae.Because of the lower abundance of the S- and UV-wavelength-sensitive cones in zebrafish, the function of arr3b remains undetermined; however, this work provides conclusive evidence that arr3a regulates high temporal resolution in high acuity color vision with experiments that are not possible in the rod-dominant mammalian retina. This work illustrates the use of the zebrafish as a vertebrate model to address the basiccellular function of cone arrestin and contributes to our broader understanding of visual processing and the complex physiology of high acuity color vision