Melanopsin and other novel mammalian opsins

Kumbalasiri, Tida; Provencio, Ignacio

doi:10.1016/j.exer.2005.05.004

Cited by 73 publications

(43 citation statements)

References 79 publications

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“…We focused on melanopsin, a Gq-coupled opsin expressed in a subset of mammalian retinal ganglion cells, which has a λ-max of ∼480 nm (Fig. 1A) (20). Using the strategy developed in Fig.…”

Section: Resultsmentioning

confidence: 99%

Optically triggering spatiotemporally confined GPCR activity in a cell and programming neurite initiation and extension

Karunarathne¹,

Giri²,

Kalyanaraman³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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G-protein-coupled receptor (GPCR) activity gradients evoke important cell behavior but there is a dearth of methods to induce such asymmetric signaling in a cell. Here we achieved reversible, rapidly switchable patterns of spatiotemporally restricted GPCR activity in a single cell. We recruited properties of nonrhodopsin opsins-rapid deactivation, distinct spectral tuning, and resistance to bleachingto activate native Gi, Gq, or Gs signaling in selected regions of a cell. Optical inputs were designed to spatiotemporally control levels of second messengers, IP3, phosphatidylinositol (3,4,5)-triphosphate, and cAMP in a cell. Spectrally selective imaging was accomplished to simultaneously monitor optically evoked molecular and cellular response dynamics. We show that localized optical activation of an opsin-based trigger can induce neurite initiation, phosphatidylinositol (3,4,5)-triphosphate increase, and actin remodeling. Serial optical inputs to neurite tips can refashion early neuron differentiation. Methods here can be widely applied to program GPCRmediated cell behaviors.optogenetics | cell polarity G -protein-coupled receptors (GPCRs) initiate most of the signaling in metazoans and regulate a wide variety of cellular responses that include differentiation, migration, secretion, and contraction. Asymmetric activation of GPCR signaling activity in a cell is thought to play a critical role in varied processes such as cell polarization (1) and modulation of neuron function (2). There is still limited information about activation of signaling that is restricted in space and time across a single cell. An impediment is the lack of methods to continuously vary signal input to a single cell with high time resolution and precision to quantitate second messenger and cellular output from the same cell. A method that provides reversible, temporal control over GPCR activity in restricted regions of a single cell may help govern cell behavior and probe the cellular and molecular basis of single-cell responses.Here we used a set of light-triggered GPCRs, human color opsins, and related nonrhodopsin opsins, to achieve such confined GPCR activation in a single cell. In contrast to molecular gradients, an optical signal provides higher spatiotemporal control and it can be switched on or off or relocated almost instantaneously. We recruited the properties of color opsins to develop optical triggers that spatiotemporally confine signaling. These opsins deactivate rapidly and demonstrate relatively low sensitivity to light (3, 4). The deactivation characteristics curtail the diffusion of activated receptors across a cell and help localize receptor activation to selected regions of a cell. Low susceptibility to bleaching allows continuous reproducible activation. In addition, nonrhodopsin opsins selectively activate different G-protein types, suggesting that they can be individually used to regulate distinct second messengers (4, 5). Rhodopsin or its chimeric forms have been valuable for globally activating G proteins (6-8). Howev...

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Section: Resultsmentioning

confidence: 99%

Optically triggering spatiotemporally confined GPCR activity in a cell and programming neurite initiation and extension

Karunarathne¹,

Giri²,

Kalyanaraman³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…These intrinsically photosensitive RGCs (ipRGCs) are now recognized as playing key roles in synchronizing circadian rhythms to the day-night cycle, mediating the pupillary response to light, and modulation of melatonin release by the pineal gland. Many aspects of this rapidly developing story have been thoroughly summarized elsewhere [4,6,14,16,31,44,54,61]. The reader is referred to these reviews for background on the intellectual origins of the discovery of melanopsin and the ipRGCs, on their structure and physiology, and on their contribution to circadian photoentrainment and other nonimage-forming visual functions.…”

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confidence: 99%

Phototransduction in ganglion-cell photoreceptors

Berson

2007

Pflugers Arch - Eur J Physiol

147

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A third class of photoreceptors has recently been identified in the mammalian retina. They are a rare cell type within the class of ganglion cells, which are the output cells of the retina. These intrinsically photosensitive retinal ganglion cells support a variety of physiological responses to daylight, including synchronization of circadian rhythms, modulation of melatonin release, and regulation of pupil size. The goal of this review is to summarize what is currently known concerning the cellular and biochemical basis of phototransduction in these cells. I summarize the overwhelming evidence that melanopsin serves as the photopigment in these cells and review the emerging evidence that the downstream signaling cascade, including the light-gated channel, might resemble those found in rhabdomeric invertebrate photoreceptors.Keywords Melanopsin . ipRGC . Photoreceptor . Rhabdomeric . Retina . Ganglion cell . Suprachiasmatic nucleus . TRPC Within the past decade, the existence of a previously unknown class of photoreceptor in the mammalian retina has come to light. These directly photosensitive neurons differ radically in form and function from the well-known rod and cone photoreceptors. They are a rare variety of retinal ganglion cells (RGCs), the class of retinal neurons sending axons through the optic nerve to synapse in the brain. For at least the prior century, it had gone without question that ganglion cells were entirely dependent on polysynaptic influences from rods and cones for their responsiveness to light (indeed, even today there is no reason to doubt this for most ganglion cells). However, as the new millennium dawned, this dogma was being challenged by behavioral studies showing the persistence of certain reflex responses to light in photoreceptor degenerate animals, e.g., [14,15,35,36], and the presence of a possible photopigment, melanopsin, in a rare population of ganglion cells [18,19,21,49,50]. In short order, it became clear that these cells possessed a capacity for autonomous phototransduction [5]. These intrinsically photosensitive RGCs (ipRGCs) are now recognized as playing key roles in synchronizing circadian rhythms to the day-night cycle, mediating the pupillary response to light, and modulation of melatonin release by the pineal gland. Many aspects of this rapidly developing story have been thoroughly summarized elsewhere [4,6,14,16,31,44,54,61]. The reader is referred to these reviews for background on the intellectual origins of the discovery of melanopsin and the ipRGCs, on their structure and physiology, and on their contribution to circadian photoentrainment and other nonimage-forming visual functions. The goal of the present review is to summarize the current state of knowledge concerning the nature of the transduction process in ipRGCs. Structural and functional properties of ipRGCs relevant to the phototransduction processThe ipRGCs represent a tiny minority of the RGCs of mammalian retinas (<1-2%) [9,21,51]. Like other ganglion cells, ipRGCs extend dendritic processes...

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“…A specialized class of opsin has emerged whose sole function is to incorporate the spent all-trans chromophore and use the energy of an absorbed photon to photoisomerize the retinoid back to the 11-cis configuration (22). The 11-cis chromophore eventually is used to regenerate the photosensory opsins, rendering them capable of initiating another round of phototransduction.…”

Section: Role Of Opn5mentioning

confidence: 99%

“…Interestingly, several published comparisons of opsin amino acid sequences have grouped Opn5 among the photoisomerases rather than the photosensory opsins (17,22,25). Furthermore, the intron:exon structure of the Opn5 gene more closely resembles that of peropsin and RGR-opsin (17).…”

Section: Role Of Opn5mentioning

confidence: 99%