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Disrupting the ciliary gradient of active Arl3 affects rod photoreceptor nuclear migration
Travis AM, Manocha S, Willer JR, Wessler TS, Skiba NP, Pearring JN
eLife. 2023, 12:e80533.
Our study shows that mutations in the small GTPase ARL3 known to cause dominant inherited human retinal dystrophies result in ARL3 hyperactivity, disrupt the normal ciliary gradient of ARL3 activity, and alter nuclear migration affecting retinal development.
The GARP Domain of the Rod CNG Channel's β1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim
Pearring JN, Martínez-Márquez J, Willer JR, Lieu EC, Salinas RY, Arshavsky VY.
Journal of Neuroscience . 2021; 41(14):3094-3104.
This image shows photoreceptor neurons in a mouse retina. A subset of rod photoreceptors are labeled with mCherry (red) and are expressing the alpha (magenta) and beta (green) subunits of the rod cyclic nucleotide-gated (CNG) channel. In the article by Pearring et al, the authors identify distinct sites encoded within the beta subunit that are used to specifically target the CNG channel to the light-sensitive outer segment compartment and subsequently sequester the CNG channel into the plasma membrane surrounding the membrane discs.
Photoreceptor discs: built like ectosomes
Spencer WJ, Lewis TR, Pearring JN, Arshavsky VY.
Trends in Cell Biology. 2020; S0962-8924(20)30165-3.
PRCD is essential for high-fidelity photoreceptor disc formation.
Spencer WJ, Ding JD,Lewis TR, Yu C, Phan S, Pearring JN, Kim KY, Thor A, Mathew R, Kalnitsky J, Hao Y,Travis AM, Biswas SK, Lo WK, Besharse JC, Ellisman MH, Saban DR, Burns ME,Arshavsky VY.
PNAS. 2019; 116(26):13087-13096.
Pictured is an electron micrograph showing accumulation of extracellular vesicles around photoreceptor cells in a mouse lacking the Prcd gene. Mutations in Prcd are a common cause of blindness in dogs and linked to retinitis pigmentosa in humans. William J. Spencer et al. found that PRCD is necessary for light-sensitive membranes of photoreceptor cells to align, flatten, and assume the shape required for efficient light capture. In the absence of PRCD, the membranes bulge and release massive amounts of extracellular vesicles, causing inflammation and retinal pathology.
Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release.
Salinas RY*, Pearring JN*, Ding JD*, Spencer WJ, Hao Y, Arshavsky VY.
Journal of Cell Biology. 2017; 216(5):1489-1499.
Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration.
Pearring JN, San Agustin JT, Lobanova ES, Gabriel CJ, Lieu EC, Monis WJ, Stuck MW, Strittmatter L, Jaber SM, Arshavsky VY, Pazour GJ.
PLoS Genetics. 2017; 13(4):e1006740.
Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants.
Ploier B, Caro LN, Morizumi T, Pandey K, Pearring JN, Goren MA, Finnemann SC, Graumann J, Arshavsky VY, Dittman JS, Ernst OP, Menon AK.
Nature Communications. 2016; 7:12832.
Progressive Rod-Cone Degeneration (PRCD) Protein Requires N-Terminal S-Acylation and Rhodopsin Binding for Photoreceptor Outer Segment Localization and Maintaining Intracellular Stability.
Spencer WJ, Pearring JN, Salinas RY, Loiselle DR, Skiba NP, Arshavsky VY.
Biochemistry. 2016; 55(36):5028-37.
De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome.
Burrage LC, Charng WL, Eldomery MK, Willer JR, Davis EE, Lugtenberg D, Zhu W, Leduc MS, Akdemir ZC, Azamian M, Zapata G, Hernandez PP, Schoots J, de Munnik SA, Roepman R, Pearring JN, Jhangiani S, Katsanis N, Vissers LE, Brunner HG, Beaudet AL, Rosenfeld JA, Muzny DM, Gibbs RA, Eng CM, Xia F, Lalani SR, Lupski JR, Bongers EM, Yang Y.
American Journal of Human Genetics. 2015; 97(6):904-13.
Guanylate cyclase 1 relies on rhodopsin for intracellular stability and ciliary trafficking.
Pearring JN, Spencer WJ, Lieu EC, Arshavsky VY.
eLife. 2015; e12058.
R9AP targeting to rod outer segments is independent of rhodopsin and is guided by the SNARE homology domain
Pearring JN, Lieu EC, Winter JR, Baker SA, Arshavsky VY.
Molecular Biology of the Cell. 2014; 25(17):2644-9.
Protein sorting, targeting and trafficking in photoreceptor cells.
Pearring JN, Salinas RY, Baker SA, Arshavsky VY.
Progress in Retinal and Eye Research. 2013; 36:24-51.
Depolarizing bipolar cell dysfunction due to a Trpm1 point mutation.
Peachey NS, Pearring JN, Bojang P Jr, Hirschtritt ME, Sturgill-Short G, Ray TA, Furukawa T, Koike C, Goldberg AF, Shen Y, McCall MA, Nawy S, Nishina PM, Gregg RG.
Journal of Neurophysiology. 2012; 108(9):2442-51.
GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness.
Peachey NS, Ray TA, Florijn R, Rowe LB, Sjoerdsma T, Contreras-Alcantara S, Baba K, Tosini G, Pozdeyev N, Iuvone PM, Bojang P Jr, Pearring JN, Simonsz HJ, van Genderen M, Birch DG, Traboulsi EI, Dorfman A, Lopez I, Ren H, Goldberg AF, Nishina PM, Lachapelle P, McCall MA, Koenekoop RK, Bergen AA, Kamermans M, Gregg RG.
American Journal of Human Genetics. 2012; 90(2):331-9.
A role for nyctalopin, a small leucine-rich repeat protein, in localizing the TRP melastatin 1 channel to retinal depolarizing bipolar cell dendrites.
Pearring JN, Bojang P Jr, Shen Y, Koike C, Furukawa T, Nawy S, Gregg RG.
Journal of Neuroscience. 2011; 31(27):10060-6.
Mutations in TRPM1 are a common cause of complete congenital stationary night blindness.
van Genderen MM, Bijveld MM, Claassen YB, Florijn RJ, Pearring JN, Meire FM, McCall MA, Riemslag FC, Gregg RG, Bergen AA, Kamermans M.
American Journal of Human Genetics. 2009; 85(5):730-6.