Matches in SemOpenAlex for { <https://semopenalex.org/work/W4285085721> ?p ?o ?g. }
- W4285085721 abstract "Tight junctions (TJs) are multiprotein complexes essential for cell polarity and the barrier function of epithelia. The major signaling molecule, protein serine/threonine phosphatase 2A (PP2A), interacts with the TJ and modulates the phosphorylation state of TJ proteins. An important PP2A regulatory mechanism involves leucine carboxyl methyltransferase-1 (LCMT1)-dependent methylation and protein phosphatase methylesterase-1 (PME1)-mediated demethylation of its catalytic subunit on Leu309. Here, using MDCK cells, we show that overexpression of LCMT1, which enhances cellular PP2A methylation, inhibits TJ formation, induces TJ ruffling, and decreases TJ barrier function. Conversely, overexpression of PME1 accelerates TJ assembly and enhances TJ barrier function. PME1-dependent PP2A demethylation increases during early Ca2+-dependent junctional assembly. Inhibition of endogenous PME1 delays the initial Ca2+-mediated redistribution of TJ proteins to cell-cell contacts and affects TJ morphology and barrier function. Manipulating one-carbon metabolism modulates TJ assembly, at least in part by affecting PP2A methylation state. The integrity of PP2A methylation is critical for proper targeting of PP2A to the TJ. It is necessary for PP2A complex formation with the TJ proteins, occludin and ZO-1, and proteins of the PAR complex, Par3 and atypical protein kinase C ζ (aPKCζ), which play a key role in development of cell polarity. Expression of a methylation incompetent PP2A mutant induces defects in TJ assembly and barrier function. aPKCζ-mediated Par3 phosphorylation is also required for targeting of the PP2A ABαC holoenzyme to the TJ. Our findings provide the first evidence for a role of LCMT1, PME1 and PP2A methylation/demethylation processes in modulating TJ assembly and functional integrity. They also position PP2A at the interface of one-carbon metabolism and the regulation of key TJ and polarity proteins that become deregulated in many human diseases." @default.
- W4285085721 created "2022-07-14" @default.
- W4285085721 creator A5052589467 @default.
- W4285085721 creator A5064294443 @default.
- W4285085721 creator A5090400274 @default.
- W4285085721 date "2022-07-13" @default.
- W4285085721 modified "2023-09-27" @default.
- W4285085721 title "A Novel Role of PP2A Methylation in the Regulation of Tight Junction Assembly and Integrity" @default.
- W4285085721 cites W13749613 @default.
- W4285085721 cites W1565516646 @default.
- W4285085721 cites W1566189373 @default.
- W4285085721 cites W1606848128 @default.
- W4285085721 cites W1738931535 @default.
- W4285085721 cites W1812864516 @default.
- W4285085721 cites W1965410387 @default.
- W4285085721 cites W1980932394 @default.
- W4285085721 cites W2012819402 @default.
- W4285085721 cites W2016510291 @default.
- W4285085721 cites W2030633377 @default.
- W4285085721 cites W2032896827 @default.
- W4285085721 cites W2034743159 @default.
- W4285085721 cites W2044830832 @default.
- W4285085721 cites W2057593147 @default.
- W4285085721 cites W2059207866 @default.
- W4285085721 cites W2059356721 @default.
- W4285085721 cites W2063618925 @default.
- W4285085721 cites W2065422003 @default.
- W4285085721 cites W2074085971 @default.
- W4285085721 cites W2074451273 @default.
- W4285085721 cites W2077774483 @default.
- W4285085721 cites W2079523306 @default.
- W4285085721 cites W2079766520 @default.
- W4285085721 cites W2084429010 @default.
- W4285085721 cites W2088811318 @default.
- W4285085721 cites W2101976554 @default.
- W4285085721 cites W2104458391 @default.
- W4285085721 cites W2110267612 @default.
- W4285085721 cites W2128154787 @default.
- W4285085721 cites W2128157486 @default.
- W4285085721 cites W2147077851 @default.
- W4285085721 cites W2153798418 @default.
- W4285085721 cites W2154555351 @default.
- W4285085721 cites W2160863855 @default.
- W4285085721 cites W2163230219 @default.
- W4285085721 cites W2165421630 @default.
- W4285085721 cites W2395973136 @default.
- W4285085721 cites W2520894026 @default.
- W4285085721 cites W2533367308 @default.
- W4285085721 cites W2612900758 @default.
- W4285085721 cites W2613054901 @default.
- W4285085721 cites W2764258509 @default.
- W4285085721 cites W2783174204 @default.
- W4285085721 cites W2810043503 @default.
- W4285085721 cites W2897750223 @default.
- W4285085721 cites W2913164636 @default.
- W4285085721 cites W2921637388 @default.
- W4285085721 cites W2939469066 @default.
- W4285085721 cites W3006856032 @default.
- W4285085721 cites W3021630345 @default.
- W4285085721 cites W3024517740 @default.
- W4285085721 cites W3036929393 @default.
- W4285085721 cites W3082443534 @default.
- W4285085721 cites W3096666331 @default.
- W4285085721 cites W3116466936 @default.
- W4285085721 cites W3119272360 @default.
- W4285085721 cites W3184556812 @default.
- W4285085721 cites W3197354418 @default.
- W4285085721 cites W3215461432 @default.
- W4285085721 doi "https://doi.org/10.3389/fcell.2022.911279" @default.
- W4285085721 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35912112" @default.
- W4285085721 hasPublicationYear "2022" @default.
- W4285085721 type Work @default.
- W4285085721 citedByCount "1" @default.
- W4285085721 countsByYear W42850857212022 @default.
- W4285085721 crossrefType "journal-article" @default.
- W4285085721 hasAuthorship W4285085721A5052589467 @default.
- W4285085721 hasAuthorship W4285085721A5064294443 @default.
- W4285085721 hasAuthorship W4285085721A5090400274 @default.
- W4285085721 hasBestOaLocation W42850857211 @default.
- W4285085721 hasConcept C104292427 @default.
- W4285085721 hasConcept C104317684 @default.
- W4285085721 hasConcept C11960822 @default.
- W4285085721 hasConcept C178666793 @default.
- W4285085721 hasConcept C185592680 @default.
- W4285085721 hasConcept C33288867 @default.
- W4285085721 hasConcept C389152 @default.
- W4285085721 hasConcept C55493867 @default.
- W4285085721 hasConcept C86803240 @default.
- W4285085721 hasConcept C95444343 @default.
- W4285085721 hasConceptScore W4285085721C104292427 @default.
- W4285085721 hasConceptScore W4285085721C104317684 @default.
- W4285085721 hasConceptScore W4285085721C11960822 @default.
- W4285085721 hasConceptScore W4285085721C178666793 @default.
- W4285085721 hasConceptScore W4285085721C185592680 @default.
- W4285085721 hasConceptScore W4285085721C33288867 @default.
- W4285085721 hasConceptScore W4285085721C389152 @default.
- W4285085721 hasConceptScore W4285085721C55493867 @default.
- W4285085721 hasConceptScore W4285085721C86803240 @default.
- W4285085721 hasConceptScore W4285085721C95444343 @default.
- W4285085721 hasFunder F4320320489 @default.