Recoverin

Philippov, Pavel P.; Zernii, Evgeni Yu

doi:10.1007/978-1-4614-6438-9_606-1

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…Recoverin is a Ca 2+ -sensor membrane-binding protein that serves as a Ca 2+ -dependent inhibitor of GRK1 in retinal rod cells. It coordinates two calcium ions by the second and the third EF-hand motifs thereby exposing its GRK1-recognizing site and N-terminal myristoyl group according to the mechanism known as a ‘Ca 2+ -myristoyl switch’ (for reviews, see Ames and Lim, 2012; Philippov and Zernii, 2012). Recoverin belongs to NCS proteins, which are expressed in the brain and retina where they transduce calcium signals in a wide range of signaling pathways and they are genetically linked to degenerative diseases (for reviews, see Burgoyne, 2007; Ames and Lim, 2012; Koch and Dell’Orco, 2015).…”

Section: Introductionmentioning

confidence: 99%

Light-Induced Thiol Oxidation of Recoverin Affects Rhodopsin Desensitization

Zernii

Nazipova

Nemashkalova

et al. 2019

Front. Mol. Neurosci.

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The excessive light illumination of mammalian retina is known to induce oxidative stress and photoreceptor cell death linked to progression of age-related macular degeneration. The photochemical damage of photoreceptors is suggested to occur via two apoptotic pathways that involve either excessive rhodopsin activation or constitutive phototransduction, depending on the light intensity. Both pathways are dramatically activated in the absence of rhodopsin desensitization by GRK1. Previously, we have shown that moderate illumination (halogen lamp, 1,500 lx, 1–5 h) of mammalian eyes provokes disulfide dimerization of recoverin, a calcium-dependent regulator of GRK1. Here, we demonstrate under in vivo conditions that both moderate long-term (metal halide lamp, 2,500 lx, 14 h, rat model) and intense short-term (halogen lamp, 30,000 lx for 3 h, rabbit model) illumination of the mammalian retina are accompanied by accumulation of disulfide dimer of recoverin. Furthermore, in the second case we reveal alternatively oxidized derivatives of the protein, apparently including its monomer with sulfinic group. Histological data indicate that thiol oxidation of recoverin precedes apoptosis of photoreceptors. Both disulfide dimer and oxidized monomer (or oxidation mimicking C39D mutant) of recoverin exhibit lowered α-helical content and thermal stability of their apo-forms, as well as increased Ca2+ affinity. Meanwhile, the oxidized monomer and C39D mutant of recoverin demonstrate impaired ability to bind photoreceptor membranes and regulate GRK1, whereas disulfide dimer exhibits notably improved membrane binding and GRK1 inhibition in absence of Ca2+. The latter effect is expected to slow down rhodopsin desensitization in the light, thereby favoring support of the light-induced oxidative stress, ultimately leading to photoreceptor apoptosis. Overall, the intensity and duration of illumination of the retina affect thiol oxidation of recoverin likely contributing to propagation of the oxidative stress and photoreceptor damage.

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Section: Introductionmentioning

confidence: 99%

Light-Induced Thiol Oxidation of Recoverin Affects Rhodopsin Desensitization

Zernii

Nazipova

Nemashkalova

et al. 2019

Front. Mol. Neurosci.

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Detection of Autoantibodies Recognizing Cancerretina Antigen Recoverin in Blood of Patients With Non-Invasive Follicular Thyroid Neoplasms With Papillary-Like Nuclear Features (Niftp)

et al. 2019

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Autoantibodies recognizing the cancer-retina autoantigen called recoverin (RCVRN-AutoAb) may serve as a highly specific biomarker of cancer-associated retinopathy. However, they may also be found in some cancer patients without clinical evidence of retinopathy. In the present study, dot-ELISA and Western blot assays were used to demonstrate the presence of circulating RCVRN-AutoAb in 4/7 (57%) of patients with recently recognized pathological entity, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP); other thyroid tumors represented by follicular adenomas, and classical and follicular variants of papillary thyroid carcinomas, demonstrated low frequencies of RCVRN-AutoAb (0/15, 1/20 (5%) and 1/15 (7%), respectively), with no significant differences from healthy individuals (0/15). Our data implicate the circulating RCVRN-AutoAb as a potential biomarker of NIFTP capable of discrimination of this novel pathological entity from other thyroid tumors.

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Recoverin

Cited by 2 publications

References 27 publications

Light-Induced Thiol Oxidation of Recoverin Affects Rhodopsin Desensitization

Light-Induced Thiol Oxidation of Recoverin Affects Rhodopsin Desensitization

Detection of Autoantibodies Recognizing Cancerretina Antigen Recoverin in Blood of Patients With Non-Invasive Follicular Thyroid Neoplasms With Papillary-Like Nuclear Features (Niftp)

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