Matches in SemOpenAlex for { <https://semopenalex.org/work/W3122662028> ?p ?o ?g. }
- W3122662028 endingPage "114427" @default.
- W3122662028 startingPage "114427" @default.
- W3122662028 abstract "Optineurin (OPTN) is a multifunctional protein that mediates a network of cellular processes regulating membrane trafficking, inflammatory responses and autophagy. The OPTN-rich interactome includes Group I metabotropic glutamate receptors (mGluR1 and 5), members of the Gαq/11 protein receptor family. Recent evidence has shown that mGluR5, in addition to its canonical Gαq/11 protein-coupled signaling, regulates autophagic machinery via mTOR/ULK1 and GSK3β/ZBTB16 pathways in both Alzheimer’s and Huntington’s disease mouse models. Despite its potential involvement, the role of OPTN in mediating mGluR5 downstream signaling cascades remains largely unknown. Here, we employed a CRISPR/Cas9 OPTN-deficient STHdhQ7/Q7 striatal cell line and global OPTN knockout mice to investigate whether Optn gene deletion alters both mGluR5 canonical and noncanonical signaling. We find that OPTN is required for mGluR5-activated Ca2+ flux and ERK1/2 signaling following receptor activation in STHdhQ7/Q7 cells and acute hippocampal slices. Deletion of OPTN impairs both GSK3β/ZBTB16 and mTOR/ULK1 autophagic signaling in STHdhQ7/Q7 cells. Furthermore, mGluR5-dependent regulation of GSK3β/ZBTB16 and mTOR/ULK1 autophagic signaling is impaired in hippocampal slices of OPTN knockout mice. Overall, we show that the crosstalk between OPTN and mGluR5 can have major implication on receptor signaling and therefore potentially contribute to the pathophysiology of neurodegenerative diseases." @default.
- W3122662028 created "2021-02-01" @default.
- W3122662028 creator A5020703324 @default.
- W3122662028 creator A5055889724 @default.
- W3122662028 creator A5061214964 @default.
- W3122662028 creator A5071625081 @default.
- W3122662028 date "2021-03-01" @default.
- W3122662028 modified "2023-09-24" @default.
- W3122662028 title "Optineurin deletion disrupts metabotropic glutamate receptor 5-mediated regulation of ERK1/2, GSK3β/ZBTB16, mTOR/ULK1 signaling in autophagy" @default.
- W3122662028 cites W1752988765 @default.
- W3122662028 cites W1895913202 @default.
- W3122662028 cites W1933410007 @default.
- W3122662028 cites W1965478144 @default.
- W3122662028 cites W1970637701 @default.
- W3122662028 cites W1975200363 @default.
- W3122662028 cites W1978849123 @default.
- W3122662028 cites W1985484942 @default.
- W3122662028 cites W1995562155 @default.
- W3122662028 cites W2000111822 @default.
- W3122662028 cites W2002636911 @default.
- W3122662028 cites W2009225398 @default.
- W3122662028 cites W2019372876 @default.
- W3122662028 cites W2019986404 @default.
- W3122662028 cites W2042567578 @default.
- W3122662028 cites W2043291430 @default.
- W3122662028 cites W2046126691 @default.
- W3122662028 cites W2046316453 @default.
- W3122662028 cites W2069910272 @default.
- W3122662028 cites W2071421185 @default.
- W3122662028 cites W2071466153 @default.
- W3122662028 cites W2076892771 @default.
- W3122662028 cites W2078884784 @default.
- W3122662028 cites W2081040572 @default.
- W3122662028 cites W2081234982 @default.
- W3122662028 cites W2083935975 @default.
- W3122662028 cites W2084719535 @default.
- W3122662028 cites W2097149963 @default.
- W3122662028 cites W2097751246 @default.
- W3122662028 cites W2101375158 @default.
- W3122662028 cites W2105911676 @default.
- W3122662028 cites W2120307371 @default.
- W3122662028 cites W2120435825 @default.
- W3122662028 cites W2120920259 @default.
- W3122662028 cites W2130632774 @default.
- W3122662028 cites W2134736026 @default.
- W3122662028 cites W2135783352 @default.
- W3122662028 cites W2136381335 @default.
- W3122662028 cites W2138730204 @default.
- W3122662028 cites W2143034003 @default.
- W3122662028 cites W2154437375 @default.
- W3122662028 cites W2154886355 @default.
- W3122662028 cites W2161584310 @default.
- W3122662028 cites W2164763690 @default.
- W3122662028 cites W2168802470 @default.
- W3122662028 cites W2169763883 @default.
- W3122662028 cites W2281751777 @default.
- W3122662028 cites W2491713134 @default.
- W3122662028 cites W2556150593 @default.
- W3122662028 cites W2584906664 @default.
- W3122662028 cites W2597685695 @default.
- W3122662028 cites W2735873011 @default.
- W3122662028 cites W2744402516 @default.
- W3122662028 cites W2769640901 @default.
- W3122662028 cites W2780161207 @default.
- W3122662028 cites W2803433687 @default.
- W3122662028 cites W2937095482 @default.
- W3122662028 cites W2967435558 @default.
- W3122662028 cites W3011757595 @default.
- W3122662028 cites W3043440868 @default.
- W3122662028 cites W3112500535 @default.
- W3122662028 cites W4241869175 @default.
- W3122662028 cites W65155625 @default.
- W3122662028 doi "https://doi.org/10.1016/j.bcp.2021.114427" @default.
- W3122662028 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33513340" @default.
- W3122662028 hasPublicationYear "2021" @default.
- W3122662028 type Work @default.
- W3122662028 sameAs 3122662028 @default.
- W3122662028 citedByCount "13" @default.
- W3122662028 countsByYear W31226620282021 @default.
- W3122662028 countsByYear W31226620282022 @default.
- W3122662028 countsByYear W31226620282023 @default.
- W3122662028 crossrefType "journal-article" @default.
- W3122662028 hasAuthorship W3122662028A5020703324 @default.
- W3122662028 hasAuthorship W3122662028A5055889724 @default.
- W3122662028 hasAuthorship W3122662028A5061214964 @default.
- W3122662028 hasAuthorship W3122662028A5071625081 @default.
- W3122662028 hasConcept C170493617 @default.
- W3122662028 hasConcept C184235292 @default.
- W3122662028 hasConcept C190283241 @default.
- W3122662028 hasConcept C203522944 @default.
- W3122662028 hasConcept C207951395 @default.
- W3122662028 hasConcept C2777801377 @default.
- W3122662028 hasConcept C2780124434 @default.
- W3122662028 hasConcept C41653306 @default.
- W3122662028 hasConcept C49051014 @default.
- W3122662028 hasConcept C54355233 @default.
- W3122662028 hasConcept C61174792 @default.
- W3122662028 hasConcept C62478195 @default.