FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4285394054> ?p ?o ?g. }

• W4285394054 endingPage "564" @default.
• W4285394054 startingPage "553" @default.
• W4285394054 abstract "Myocilin is secreted from trabecular meshwork cells to an eponymous extracellular matrix that is critical for maintaining intraocular pressure. Missense mutations found in the myocilin olfactomedin domain (OLF) lead to intracellular myocilin misfolding and are causative for the heritable form of early-onset glaucoma. The OLF domain contains a unique internal, hetero-dinuclear calcium site. Here, we tested the hypothesis that calcium dysregulation causes wild-type (WT) myocilin misfolding reminiscent of that observed for disease variants. Using two cellular models expressing WT myocilin, we show that the Ca2+ ATPase channel blocker thapsigargin inhibits WT myocilin secretion. Intracellular WT myocilin is at least partly insoluble and aggregated in the endoplasmic reticulum (ER), and stains positively with an amyloid dye. By comparing the effect of thapsigargin on WT myocilin to that on a de novo secretion-competent Ca2+-free variant D478S, we discern that non-secretion of WT myocilin is due initially to calcium dysregulation, and is potentiated further by resultant ER stress. In E. coli, depletion of calcium leads to recombinant expression of misfolded isolated WT OLF but the D478S variant is still produced as a folded monomer. Treatment of cells expressing a double mutant composed of D478S and either disease variants P370L or Y437H with thapsigargin promotes its misfolding and aggregation, demonstrating the limits of D478S to correct secretion defects. Taken together, the heterodinuclear calcium site is a liability for proper folding of myocilin. Our study suggests a molecular mechanism by which WT myocilin misfolding may contribute broadly to glaucoma-associated ER stress. This study explores the effect of calcium depletion on myocilin olfactomedin domain folding." @default.
• W4285394054 created "2022-07-14" @default.
• W4285394054 creator A5015701036 @default.
• W4285394054 creator A5053923906 @default.
• W4285394054 creator A5059220047 @default.
• W4285394054 creator A5075604712 @default.
• W4285394054 creator A5078617713 @default.
• W4285394054 creator A5086112277 @default.
• W4285394054 date "2022-07-13" @default.
• W4285394054 modified "2023-10-14" @default.
• W4285394054 title "Calcium dysregulation potentiates wild-type myocilin misfolding: implications for glaucoma pathogenesis" @default.
• W4285394054 cites W1485297825 @default.
• W4285394054 cites W1534476597 @default.
• W4285394054 cites W1593385535 @default.
• W4285394054 cites W1595351482 @default.
• W4285394054 cites W1605473834 @default.
• W4285394054 cites W1697178647 @default.
• W4285394054 cites W1798182214 @default.
• W4285394054 cites W1996110784 @default.
• W4285394054 cites W1998916177 @default.
• W4285394054 cites W2009189021 @default.
• W4285394054 cites W2012801606 @default.
• W4285394054 cites W2017996813 @default.
• W4285394054 cites W2022050193 @default.
• W4285394054 cites W2028262585 @default.
• W4285394054 cites W2036145275 @default.
• W4285394054 cites W2052524483 @default.
• W4285394054 cites W2062536374 @default.
• W4285394054 cites W2064417092 @default.
• W4285394054 cites W2067155379 @default.
• W4285394054 cites W2069880676 @default.
• W4285394054 cites W2071186324 @default.
• W4285394054 cites W2072365851 @default.
• W4285394054 cites W2073798474 @default.
• W4285394054 cites W2078077142 @default.
• W4285394054 cites W2081646244 @default.
• W4285394054 cites W2088832238 @default.
• W4285394054 cites W2100159037 @default.
• W4285394054 cites W2109395212 @default.
• W4285394054 cites W2110310702 @default.
• W4285394054 cites W2113044948 @default.
• W4285394054 cites W2115935336 @default.
• W4285394054 cites W2124733101 @default.
• W4285394054 cites W2128489958 @default.
• W4285394054 cites W2129856680 @default.
• W4285394054 cites W2133989466 @default.
• W4285394054 cites W2137559379 @default.
• W4285394054 cites W2145192598 @default.
• W4285394054 cites W2154759985 @default.
• W4285394054 cites W2167778036 @default.
• W4285394054 cites W2405114694 @default.
• W4285394054 cites W2419484061 @default.
• W4285394054 cites W2499240546 @default.
• W4285394054 cites W2951352684 @default.
• W4285394054 cites W2955742566 @default.
• W4285394054 cites W2998974209 @default.
• W4285394054 cites W3000547714 @default.
• W4285394054 cites W3165670002 @default.
• W4285394054 cites W4231059664 @default.
• W4285394054 cites W4255760236 @default.
• W4285394054 cites W843844753 @default.
• W4285394054 cites W3153024404 @default.
• W4285394054 doi "https://doi.org/10.1007/s00775-022-01946-3" @default.
• W4285394054 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35831671" @default.
• W4285394054 hasPublicationYear "2022" @default.
• W4285394054 type Work @default.
• W4285394054 citedByCount "2" @default.
• W4285394054 countsByYear W42853940542023 @default.
• W4285394054 crossrefType "journal-article" @default.
• W4285394054 hasAuthorship W4285394054A5015701036 @default.
• W4285394054 hasAuthorship W4285394054A5053923906 @default.
• W4285394054 hasAuthorship W4285394054A5059220047 @default.
• W4285394054 hasAuthorship W4285394054A5075604712 @default.
• W4285394054 hasAuthorship W4285394054A5078617713 @default.
• W4285394054 hasAuthorship W4285394054A5086112277 @default.
• W4285394054 hasBestOaLocation W42853940542 @default.
• W4285394054 hasConcept C104317684 @default.
• W4285394054 hasConcept C139447449 @default.
• W4285394054 hasConcept C143065580 @default.
• W4285394054 hasConcept C158617107 @default.
• W4285394054 hasConcept C169760540 @default.
• W4285394054 hasConcept C178790620 @default.
• W4285394054 hasConcept C185592680 @default.
• W4285394054 hasConcept C207583985 @default.
• W4285394054 hasConcept C2777146706 @default.
• W4285394054 hasConcept C2778527774 @default.
• W4285394054 hasConcept C2781121420 @default.
• W4285394054 hasConcept C2781147369 @default.
• W4285394054 hasConcept C28406088 @default.
• W4285394054 hasConcept C49039625 @default.
• W4285394054 hasConcept C519063684 @default.
• W4285394054 hasConcept C55493867 @default.
• W4285394054 hasConcept C86803240 @default.
• W4285394054 hasConcept C95444343 @default.
• W4285394054 hasConceptScore W4285394054C104317684 @default.
• W4285394054 hasConceptScore W4285394054C139447449 @default.
• W4285394054 hasConceptScore W4285394054C143065580 @default.
• W4285394054 hasConceptScore W4285394054C158617107 @default.

• next