Differential adaptations in rod outer segment disc membranes in different models of congenital stationary night blindness

Senapati, Subhadip; Park, Paul S.‐H.

doi:10.1016/j.bbamem.2020.183396

Cited by 5 publications

(10 citation statements)

References 54 publications

(118 reference statements)

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“…These observations are consistent with observations made in the photoreceptor cells of Rpe65 –/– mice, where rhodopsin is present in the apoprotein opsin form. Photoreceptors cells in these mice properly form outer segments where the apoprotein opsin is organized as oligomers forming nanodomains within the disc membrane …”

Section: Discussionmentioning

confidence: 99%

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Differential Aggregation Properties of Mutant Human and Bovine Rhodopsin

Vasudevan

Park

2020

Biochemistry

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Rhodopsin is the light receptor required for the function and health of photoreceptor cells. Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinal degeneration. Bovine rhodopsin is often used as a model to understand the effect of pathogenic mutations in rhodopsin due to the abundance of structural information on the bovine form of the receptor. It is unclear whether or not the bovine rhodopsin template is adequate in predicting the effect of these mutations occurring in human retinal disease or in predicting the efficacy of therapeutic strategies. To better understand the extent to which bovine rhodopsin can serve as a model, human and bovine P23H rhodopsin mutants expressed heterologously in cells were examined. The aggregation properties and cellular localization of the mutant receptors were determined by Forster resonance energy transfer and confocal microscopy. The potential therapeutic effects of the pharmacological compounds 9-cis retinal and metformin were also examined. Human and bovine P23H rhodopsin mutants exhibited different aggregation properties and responses to the pharmacological compounds tested. These observations would lead to different predictions on the severity of the phenotype and divergent predictions on the benefit of the therapeutic compounds tested. The bovine rhodopsin template does not appear to adequately model the effects of the P23H mutation in the human form of the receptor.

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Section: Discussionmentioning

confidence: 99%

“…Photoreceptors cells in these mice properly form outer segments where the apoprotein opsin is organized as oligomers forming nanodomains within the disc membrane. 41 Properties of P23H Rhodopsin. The amount of the endogenous ligand 11-cis retinal is stoichiometric with the rhodopsin protein in the retina.…”

Section: ■ Discussionmentioning

confidence: 99%

Differential Aggregation Properties of Mutant Human and Bovine Rhodopsin

Vasudevan

Park

2020

Biochemistry

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“…[27,28] Follow-up AFM studies have consistently shown small domain-like structures with nanoscale dimensions, which we later termed 'nanodomains'. [38,40,41,[43][44][45][46]55,56] These nanodomains were also shown to consist of rhodopsin dimers, [28] and were further characterized for the presence of rhodopsin by an AFMimmunolabeling study. [56] The functional aspects of the dimeric organization and nanodomains are still unclear and yet to be established.…”

Section: Nanoscale Analysis Of Rhodopsin Present In Native Disc Membr...mentioning

confidence: 99%

“…Quantitative assessment of disc membrane properties due to adaptations in response to lighting conditions, [45] DHA-modulation, [43] and diseased states. [41] Source of disc membrane [45] Wild-type (10 days dark) [45] Wild-type (20 days dark) a [45] Wild-type (30 days dark) a [45] Wild-type (dark-reared) b [45] DHA-deficient (cyclic) [43] DHA-adequate (cyclic) [43] DHA-replenished (cyclic) 1.30 � 0.36 [43] Rho-G90D Senapati and Park (2020) [41] [a]…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

“…[40] AFM imaging has helped us to characterize the disc membranes, and quantify the rhodopsin content/density, giving us further insights into how rhodopsin achieves its supramolecular structure and factors that can modulate this organization. [38,[41][42][43][44][45][46] We adopted single-molecule force spectroscopy (SMFS) and dynamic SMFS (DFS) techniques to quantify and localize molecular interactions that stabilize the structure of rhodopsin and direct its function as membrane proteins in normal (wild-type) and diseased states (constitutive activity). [39,47,48] Finally, we utilized the nanoindentation method to measure and map the changes in rhodopsin stiffness for normal and diseased states, and explored different models for constitutive activity based on the stiffness data.…”

Section: Introductionmentioning

confidence: 99%

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Understanding the Rhodopsin Worldview Through Atomic Force Microscopy (AFM): Structure, Stability, and Activity Studies

Senapati

Park

2023

The Chemical Record

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Rhodopsin is a G protein‐coupled receptor (GPCR) present in the rod outer segment (ROS) of photoreceptor cells that initiates the phototransduction cascade required for scotopic vision. Due to the remarkable advancements in technological tools, the chemistry of rhodopsin has begun to unravel especially over the past few decades, but mostly at the ensemble scale. Atomic force microscopy (AFM) is a tool capable of providing critical information from a single‐molecule point of view. In this regard, to bolster our understanding of rhodopsin at the nanoscale level, AFM‐based imaging, force spectroscopy, and nano‐indentation techniques were employed on ROS disc membranes containing rhodopsin, isolated from vertebrate species both in normal and diseased states. These AFM studies on samples from native retinal tissue have provided fundamental insights into the structure and function of rhodopsin under normal and dysfunctional states. We review here the findings from these AFM studies that provide important insights on the supramolecular organization of rhodopsin within the membrane and factors that contribute to this organization, the molecular interactions stabilizing the structure of the receptor and factors that can modify those interactions, and the mechanism underlying constitutive activity in the receptor that can cause disease.

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Supramolecular organization of rhodopsin in rod photoreceptor cell membranes

Park

2021

Pflugers Arch - Eur J Physiol

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Differential adaptations in rod outer segment disc membranes in different models of congenital stationary night blindness

Cited by 5 publications

References 54 publications

Differential Aggregation Properties of Mutant Human and Bovine Rhodopsin

Differential Aggregation Properties of Mutant Human and Bovine Rhodopsin

Understanding the Rhodopsin Worldview Through Atomic Force Microscopy (AFM): Structure, Stability, and Activity Studies

Supramolecular organization of rhodopsin in rod photoreceptor cell membranes

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