% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Yamoah:1006648, author = {Yamoah, Alfred and Tripathi, Priyanka and Guo, Haihong and Scheve, Leonie and Walter, Peter and Johnen, Sandra and Müller, Frank and Weis, Joachim and Goswami, Anand}, title = {{E}arly {A}lterations of {RNA} {B}inding {P}rotein ({RBP}) {H}omeostasis and {ER} {S}tress-{M}ediated {A}utophagy {C}ontributes to {P}rogressive {R}etinal {D}egeneration in the rd10 {M}ouse {M}odel of {R}etinitis {P}igmentosa ({RP})}, journal = {Cells}, volume = {12}, number = {7}, issn = {2073-4409}, address = {Basel}, publisher = {MDPI}, reportid = {FZJ-2023-01780}, pages = {1094}, year = {2023}, note = {This research was supported by the DFG grants, WE1406/14-3 to J.W., WE 1406/16-1 to J.W.and A.G., MU-3036/3-3 to F.M.,WA-1472/6-3 to P.W., and JO-1263/1-3 to S.J., by the InterdisciplinaryCentre for Clinical Research (IZKF Aachen, N7-4, to A.G. and J.W.) and by the EU Joint ProgramNeurodegenerative Disease Research (JPND, Fly-SMALS, to J.W.).}, abstract = {The retinal degeneration 10 (rd10) mouse model is widely used to study retinitis pigmentosa(RP) pathomechanisms. It offers a rather unique opportunity to study trans-neuronal degenerationbecause the cell populations in question are separated anatomically and the mutated Pde6b gene isselectively expressed in rod photoreceptors. We hypothesized that RNA binding protein (RBP) aggregationand abnormal autophagy might serve as early pathogenic events, damaging non-photoreceptorretinal cell types that are not primarily targeted by the Pde6b gene defect. We used a combination ofimmunohistochemistry (DAB, immunofluorescence), electron microscopy (EM), subcellular fractionation,andWestern blot analysis on the retinal preparations obtained from both rd10 and wild-typemice. We found early, robust increases in levels of the protective endoplasmic reticulum (ER) calcium(Ca2+) buffering chaperone Sigma receptor 1 (SigR1) together with other ER-Ca2+ buffering proteinsin both photoreceptors and non-photoreceptor neuronal cells before any noticeable photoreceptordegeneration. In line with this, we found markedly altered expression of the autophagy proteinsp62 and LC3, together with abnormal ER widening and large autophagic vacuoles as detected byEM. Interestingly, these changes were accompanied by early, prominent cytoplasmic and nuclearaggregation of the key RBPs including pTDP-43 and FET family RBPs and stress granule formation.We conclude that progressive neurodegeneration in the rd10 mouse retina is associated with earlydisturbances of proteostasis and autophagy, along with abnormal cytoplasmic RBP aggregation.}, cin = {IBI-1}, ddc = {570}, cid = {I:(DE-Juel1)IBI-1-20200312}, pnm = {5241 - Molecular Information Processing in Cellular Systems (POF4-524)}, pid = {G:(DE-HGF)POF4-5241}, typ = {PUB:(DE-HGF)16}, pubmed = {37048167}, UT = {WOS:000969574200001}, doi = {10.3390/cells12071094}, url = {https://juser.fz-juelich.de/record/1006648}, }