Recoverin

Last updated

RCVRN
Recov.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RCVRN , RCV1, recoverin, Recoverin
External IDs OMIM: 179618; MGI: 97883; HomoloGene: 2177; GeneCards: RCVRN; OMA:RCVRN - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002903

NM_009038

RefSeq (protein)

NP_002894

NP_033064

Location (UCSC) Chr 17: 9.9 – 9.91 Mb Chr 11: 67.59 – 67.59 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Recoverin (abbreviated Recov) is a 23 kilodalton (kDa) neuronal calcium-binding protein that is primarily detected in the photoreceptor cells of the eye. [5] It plays a key role in the inhibition of rhodopsin kinase, a molecule which regulates the phosphorylation of rhodopsin. [6] A reduction in this inhibition helps regulate sensory adaptation in the retina, since the light-dependent channel closure in photoreceptors causes calcium levels to decrease, which relieves the inhibition of rhodopsin kinase by calcium-bound recoverin, leading to a more rapid inactivation of metarhodopsin II (activated form of rhodopsin).

Contents

Structure

Recoverin structure consists of four EF-hand motifs arranged in a compact array, which contrasts with the dumbbell shape of other calcium-binding proteins like calmodulin and troponin C. [7]

Recoverin undergoes a conformational change in a [Ca2+]-dependent way. This protein is myristoylated at its amino-terminal. [8] The myristoyl group is sequestered in a hydrophobic cavity of the protein in its Ca2+-unbound form. Upon binding of recoverin to Ca2+, the group is extruded and inserted into rod membranes, [9] probably facilitating the interaction with membrane-bound GRK1. Specific amino acid residues become exposed to the surface of the recoverin molecule or relocate, possibly forming a site to inhibit GRK1 [10] [11] Solution structures of myristoylated recoverin with and without bound Ca2+ have been reported. [12] [13]

Function

The vertebrate retina contains two types of photoreceptors: rods and cones. Rods have been studied more intensively than cones due to their simpler preparation. A rod responds to light by generating a hyperpolarizing electrical response (light response) via the phototransduction cascade located in the rod's outer segment (OS). Rods adapt to varying light conditions by decreasing their sensitivity to prevent saturation, thus enhancing their functionality across a range of ambient light intensities. This process, termed light adaptation, involves modifications to the phototransduction cascade that occur under reduced [Ca2+] levels in the rod OS during light exposure. [14] The first step in this cascade is the absorption of light by visual pigments. An activated rhodopsin (Rh*) stimulates approximately 100 transducin molecules per second, initiating the cascade. After activating phototransduction, Rh* must be inactivated. Although Rh* naturally decays over time, rhodopsin kinase (GRK1) quenches it more rapidly through phosphorylation. Recoverin plays a role in this process by inhibiting the phosphorylation of Rh* at high [Ca2+] levels [15] ) by binding to GRK1 rather than Rh*,{ [16] thereby extending the lifetime of Rh*. Understanding the role of recoverin in light adaptation requires noting that [Ca2+] is high in darkness and low under light conditions in the OS. [17] Consequently, a flash of light in the dark triggers a prolonged response since recoverin at high [Ca2+] inhibits GRK1, resulting in a longer lifetime for Rh*.

Physiological studies revealed that injection of recoverin into Gecko rods lengthened the flash response duration, [18] while its deletion in mouse rods reduced it, [19] aligning with expectations. However, the study in mice revealed that recoverin deletion affects neither the rising phase of a light response nor the response peak (time and amplitude) and facilitates the response recovery time course to shorten the duration. These results can be explained when the phosphorylation of Rh* occurs around or just after the peak of a response in rods. [20] (The phosphorylation in cones is likely to take place before the response reaches its peak.)

Since the response amplitude determines photoreceptor light sensitivity, recoverin minimally affects the sensitivity to a single flash in the wild-type mouse. However, under continuous light, the response amplitude, and thus the sensitivity, is lower in mice lacking recoverin compared to wild-type mice. [19] This decrease is probably due to a temporal accumulation of single flash responses of shorter duration with unaltered peak amplitude at lowered [Ca2+].

In the dark, approximately 10% of total recoverin in the mouse retina is present in the rod OS, and the rest is distributed throughout the rod cell. [21] Under light, those in the OS translocate towards rod synaptic terminals, suggesting recoverin may have roles in addition to controlling Rh* lifetime, such as enhancing signal transmission from rods to rod bipolar cells. [22] Recoverin is also an antigen of cancer-associated retinopathy. [23]

Discovery

Two proteins, recoverin in bovine and its frog ortholog, S-modulin, were reported in 1991 as proteins involved in light-adaptation in rod photoreceptors. [24] [25]

Related Research Articles

<span class="mw-page-title-main">Calmodulin</span> Messenger protein

Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of calmodulin. Once bound to Ca2+, calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases.

<span class="mw-page-title-main">Transducin</span>

Transducin (Gt) is a protein naturally expressed in vertebrate retina rods and cones and it is very important in vertebrate phototransduction. It is a type of heterotrimeric G-protein with different α subunits in rod and cone photoreceptors.

<span class="mw-page-title-main">Rod cell</span> Photoreceptor cells that can function in lower light better than cone cells

Rod cells are photoreceptor cells in the retina of the eye that can function in lower light better than the other type of visual photoreceptor, cone cells. Rods are usually found concentrated at the outer edges of the retina and are used in peripheral vision. On average, there are approximately 92 million rod cells in the human retina. Rod cells are more sensitive than cone cells and are almost entirely responsible for night vision. However, rods have little role in color vision, which is the main reason why colors are much less apparent in dim light.

In visual physiology, adaptation is the ability of the retina of the eye to adjust to various levels of light. Natural night vision, or scotopic vision, is the ability to see under low-light conditions. In humans, rod cells are exclusively responsible for night vision as cone cells are only able to function at higher illumination levels. Night vision is of lower quality than day vision because it is limited in resolution and colors cannot be discerned; only shades of gray are seen. In order for humans to transition from day to night vision they must undergo a dark adaptation period of up to two hours in which each eye adjusts from a high to a low luminescence "setting", increasing sensitivity hugely, by many orders of magnitude. This adaptation period is different between rod and cone cells and results from the regeneration of photopigments to increase retinal sensitivity. Light adaptation, in contrast, works very quickly, within seconds.

<span class="mw-page-title-main">Retinal</span> Vitamin A aldehyde, a polyene chromophore

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<span class="mw-page-title-main">Melanopsin</span> Mammalian protein found in Homo sapiens

Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.

Visual phototransduction is the sensory transduction process of the visual system by which light is detected by photoreceptor cells in the vertebrate retina. A photon is absorbed by a retinal chromophore, which initiates a signal cascade through several intermediate cells, then through the retinal ganglion cells (RGCs) comprising the optic nerve.

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Hippocalcin is a protein that in humans is encoded by the HPCA gene.

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<span class="mw-page-title-main">Lubert Stryer</span> American biochemist (1938–2024)

Lubert Stryer was an American academic who was the Emeritus Mrs. George A. Winzer Professor of Cell Biology, at Stanford University School of Medicine. His research over more than four decades had been centered on the interplay of light and life. In 2007 he received the National Medal of Science from President Bush at a ceremony at the White House for elucidating the biochemical basis of signal amplification in vision, pioneering the development of high density microarrays for genetic analysis, and authoring the standard undergraduate biochemistry textbook, Biochemistry. It is now in its tenth edition and also edited by Jeremy Berg, Justin Hines, John L. Tymoczko and Gregory J. Gatto, Jr.

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<span class="mw-page-title-main">Congenital stationary night blindness</span> Medical condition

Congenital stationary night blindness (CSNB) is a rare non-progressive retinal disorder. People with CSNB often have difficulty adapting to low light situations due to impaired photoreceptor transmission. These patients may also have reduced visual acuity, myopia, nystagmus, fundus abnormalities, and strabismus. CSNB has two forms -- complete, also known as type-1 (CSNB1), and incomplete, also known as type-2 (CSNB2), which are distinguished by the involvement of different retinal pathways. In CSNB1, downstream neurons called bipolar cells are unable to detect neurotransmission from photoreceptor cells. CSNB1 can be caused by mutations in various genes involved in neurotransmitter detection, including NYX. In CSNB2, the photoreceptors themselves have impaired neurotransmission function; this is caused primarily by mutations in the gene CACNA1F, which encodes a voltage-gated calcium channel important for neurotransmitter release. CSNB has been identified in horses and dogs as the result of mutations in TRPM1, GRM6, and LRIT3 .

Rhodopsin kinase is a serine/threonine-specific protein kinase involved in phototransduction. This enzyme catalyses the following chemical reaction:

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References

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