rhodopsin

Bestrhodopsins constitute a class of light-regulated pentameric ion channels that consist of one or two rhodopsins in tandem fused with bestrophin ion channel domains. Here, we report on the isomerization dynamics in the rhodopsin tandem domains of Phaeocystis antarctica bestrhodopsin, which binds all-trans retinal Schiff-base (RSB) absorbing at 661 nm and, upon illumination, converts to the meta-stable P540 state with an unusual 11- cis RSB. The primary photoproduct P682 corresponds to a mixture of highly distorted 11 -cis and 13- cis RSB directly formed from the excited state in 1...

Retinopathy caused by ultraviolet radiation and cancer chemotherapy has increased dramatically in humans due to rapid environmental and social changes. Therefore, it is very important to develop therapeutic strategies to effectively alleviate retinopathy. In China, people often choose dendrobium to improve their eyesight. In this study, we explored how Dendrobium fimbriatum extract (DFE) protects ARPE-19 cells and mouse retinal tissue from damage of ultraviolet (UV) radiation and chemotherapy. We evaluated the antioxidant capacity of DFE using the 1,1-diphenyl-2-trinitophenylhydrazine (DPPH) assay...

Ligand-triggered activation of G protein-coupled receptors (GPCRs) relies on the phenomenon of loose allosteric coupling, which involves conformational alterations spanning from the extracellular ligand-binding domain to the cytoplasmic region, where interactions with G proteins occur. During the GPCR activation process, several intermediate and equilibrium states orchestrate the movement of the flexible and rigid transmembrane (TM) segments of the GPCR. Monitoring early conformational changes is important in unraveling the structural intricacies of the loose allosteric coupling...

Evolutionary convergences are observed at all levels, from phenotype to DNA and protein sequences, and changes at these different levels tend to be correlated. Notably, convergent mutations can lead to convergent changes in phenotype, such as changes in metabolism, drug resistance, and other adaptations to changing environments. We propose a two-component approach to detect mutations subject to convergent evolution in protein alignments. The "Emergence" component selects mutations that emerge more often than expected, while the "Correlation" component selects mutations that correlate with the convergent phenotype under study...

Retinitis pigmentosa (RP) is a common form of retinal dystrophy that can be caused by mutations in any one of dozens of rod photoreceptor genes. The genetic heterogeneity of RP represents a significant challenge for the development of effective therapies. Here, we present evidence for a potential gene-independent therapeutic strategy based on targeting Nr2e3 , a transcription factor required for the normal differentiation of rod photoreceptors. Nr2e3 knockout results in hybrid rod photoreceptors that express the full complement of rod genes, but also a subset of cone genes...

NUDC (nuclear distribution protein C) is a mitotic protein involved in nuclear migration and cytokinesis across species. Considered a cytoplasmic dynein (henceforth dynein) cofactor, NUDC was shown to associate with the dynein motor complex during neuronal migration. NUDC is also expressed in postmitotic vertebrate rod photoreceptors where its function is unknown. Here, we examined the role of NUDC in postmitotic rod photoreceptors by studying the consequences of a conditional NUDC knockout in mouse rods (rNudC-/- )...

The properties of a prosthetic group are broadened by interactions with its neighboring residues in proteins. The retinal chromophore in rhodopsins absorbs light, undergoes structural changes, and drives functionally important structural changes in proteins during the photocycle. It is therefore crucial to understand how chromophore-protein interactions regulate the molecular structure and electronic state of chromophores in rhodopsins. Schizorhodopsin is a newly discovered subfamily of rhodopsins found in the genomes of Asgard archaea, which are extant prokaryotes closest to the last common ancestor of eukaryotes and of other microbial species...

OBJECTIVES: Glaucoma is a leading cause of irreversible blindness, and effective therapies to reverse the visual system damage caused by glaucoma are still lacking. Recently, the stem cell therapy enable the repair and regeneration of the damaged retinal neurons, but challenges regarding the source of stem cells remain. This study aims to investigate a protocol that allows the dedifferentiation of Müller cells into retinal stem cells, following by directed differentiation into retinal ganglion cells with high efficiency, and to provide a new method of cellular acquisition for retinal stem cells...

The neuropeptide Y4 receptor (Y4 R), a rhodopsin-like G protein-coupled receptor (GPCR) and the hormone pancreatic polypeptide (PP) are members of the neuropeptide Y family consisting of four receptors (Y1 R, Y2 R, Y4 R, Y5 R) and three highly homologous peptide ligands (neuropeptide Y, peptide YY, PP). In this family, the Y4 R is of particular interest as it is the only subtype with high affinity to PP over NPY. The Y4 R, as a mediator of PP signaling, has a pivotal role in appetite regulation and energy homeostasis, offering potential avenues for the treatment of metabolic disorders such as obesity...

Vision is mainly based on two different tasks, object detection and color discrimination through activities of photoreceptor (PR) cells. Drosophila compound eye consists of ∼800 ommatidia. Every ommatidium contains eight PR cells; six outer cells (R1-R6) and two inner cells (R7 and R8) by which object detection and color vision are achieved, respectively. Expression of opsin genes in R7 and R8 is highly coordinated through the instructive signal from R7 to R8, and two major ommatidial subtypes are distributed stochastically; pale type expresses Rh3/Rh5, while yellow type expresses Rh4/Rh6 in R7/R8...

A delicate balance between photon absorption for vision and protection of photoreceptors from light damage is pivotal for ocular health. This equilibrium is governed by the light-absorbing 11-cis-retinylidene chromophore of visual pigments, which, upon bleaching, transforms into all-trans-retinal and undergoes regeneration through an enzymatic pathway, named the visual cycle. Chemical side reactions of retinaldehydes during the recycling process can generate byproducts that may result in a depletion of retinoids...

The bioavailability and toxicity of organic pollutants in aquatic organisms can be largely affected by the co-existed nanoparticles. However, the impacts of such combined exposure on the visual system remain largely unknown. Here, we systematically investigated the visual toxicity in zebrafish larvae after single or joint exposure to titanium dioxide nanoparticles (n-TiO2 ) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) at environmentally relevant levels. Molecular dynamics simulations revealed the enhanced transmembrane capability of the complex than the individual, which accounted for the increased bioavailability of both TBPH and n-TiO2 when combined exposure to zebrafish...

Microbial rhodopsin (MRs) ion channels and pumps have become invaluable optogenetic tools for neuroscience as well as biomedical applications. Recently, MR-optogenetics expanded towards subcellular organelles opening principally new opportunities in optogenetic control of intracellular metabolism and signaling via precise manipulations of organelle ion gradients using light. This new optogenetic field expands the opportunities for basic and medical studies of cancer, cardiovascular, and metabolic disorders, providing more detailed and accurate control of cell physiology...

Optogenetics, a technique that employs light for neuromodulation, has revolutionized the study of neural mechanisms and the treatment of neurological disorders due to its high spatiotemporal resolution and cell-type specificity. However, visible light, particularly blue and green light, commonly used in conventional optogenetics, has limited penetration in biological tissue. This limitation necessitates the implantation of optical fibers for light delivery, especially in deep brain regions, leading to tissue damage and experimental constraints...

Retinitis pigmentosa (RP) is a form of retinal degeneration characterized by primary degeneration of rod photoreceptors followed by a secondary cone loss that leads to vision impairment and finally blindness. This is a rare disease with mutations in several genes and high genetic heterogeneity. A challenging effort has been the characterization of the molecular mechanisms underlying photoreceptor cell death during the progression of the disease. Some of the cell death pathways have been identified and comprise stress events found in several neurodegenerative diseases such as oxidative stress, inflammation, calcium imbalance and endoplasmic reticulum stress...

Mutations in the Rhodopsin (RHO) gene are the predominant causes of autosomal dominant retinitis pigmentosa (adRP). Given the diverse gain-of-function mutations, therapeutic strategies targeting specific sequences face significant challenges. Here, we provide a universal approach to conquer this problem: we have devised a CRISPR-Cas12i-based, mutation-independent gene knockout and replacement compound therapy carried by a dual AAV8 system. In this study, we successfully delayed the progression of retinal degeneration in the classic mouse disease model Rho P23H , and also Rho P347S , a new native mouse mutation model we developed...

The rediscovery of diatom blooms embedded within and beneath Lake Erie ice cover (2007-2012) ignited interest in psychrophilic adaptations and winter limnology. Subsequent studies determined ice plays a vital role in winter diatom ecophysiology, as diatoms partition to the underside of ice thereby fixing their location within the photic zone. Yet, climate change has led to widespread ice decline across the Great Lakes, with Lake Erie presenting a nearly "ice-free" state in several recent winters. It has been hypothesized the resultant turbid, isothermal water column will induce light limitation amongst winter diatoms, serving as a detrimental competitive disadvantage...

Mutations in rhodopsin can cause it to misfold and lead to retinal degeneration. A distinguishing feature of these mutants in vitro is that they mislocalize and aggregate. It is unclear whether or not these features contribute to retinal degeneration observed in vivo. The effect of P23H and G188R misfolding mutations were examined in a heterologous expression system and knockin mouse models, including a mouse model generated here expressing the G188R rhodopsin mutant. In vitro characterizations demonstrate that both mutants aggregate, with the G188R mutant exhibiting a more severe aggregation profile compared to the P23H mutant...

Here, we present the draft genome sequences of three Croceitalea sp. strains containing microbial rhodopsins, isolated from the Japanese coastal sea surface microlayer, which is exposed to intense sunlight. This study will contribute to the understanding of the genus Croceitalea and the diversity of microbial rhodopsins.

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