FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4297221207> ?p ?o ?g. }

• W4297221207 endingPage "4214" @default.
• W4297221207 startingPage "4197" @default.
• W4297221207 abstract "Abstract The skeletal muscle Ca V 1.1 channel functions as the voltage‐sensor of excitation−contraction (EC) coupling. Recently, the adaptor protein STAC3 was found to be essential for both Ca V 1.1 functional expression and EC coupling. Interestingly, STAC proteins were also reported to inhibit calcium‐dependent inactivation (CDI) of L‐type calcium channels (LTCC), an important negative feedback mechanism in calcium signaling. The same could not be demonstrated for Ca V 1.1, as STAC3 is required for its functional expression. However, upon strong membrane depolarization, Ca V 1.1 conducts calcium currents characterized by very slow kinetics of activation and inactivation. Therefore, we hypothesized that the negligible inactivation observed in Ca V 1.1 currents reflects the inhibitory effect of STAC3. Here, we inserted a triple mutation in the linker region of STAC3 (ETLAAA), as the analogous mutation abolished the inhibitory effect of STAC2 on CDI of Ca V 1.3 currents. When coexpressed in Ca V 1.1/STAC3 double knockout myotubes, the mutant STAC3‐ETLAAA failed to colocalize with Ca V 1.1 in the sarcoplasmic reticulum/membrane junctions. However, combined patch‐clamp and calcium recording experiments revealed that STAC3‐ETLAAA supports Ca V 1.1 functional expression and EC coupling, although at a reduced extent compared to wild‐type STAC3. Importantly, STAC3‐ETLAAA coexpression dramatically accelerated the kinetics of activation and inactivation of Ca V 1.1 currents, suggesting that STAC3 determines the slow Ca V 1.1 currents kinetics. To examine if STAC3 specifically inhibits the CDI of Ca V 1.1 currents, we performed patch‐clamp recordings using calcium and barium as charge carriers in HEK cells. While Ca V 1.1 displayed negligible CDI with STAC3, this did not increase in the presence of STAC3‐ETLAAA. On the contrary, our data demonstrate that STAC3 specifically inhibits the voltage‐dependent inactivation (VDI) of Ca V 1.1 currents. Altogether, these results designate STAC3 as a crucial determinant for the slow activation kinetics of Ca V 1.1 currents and implicate STAC proteins as modulators of both components of inactivation of LTCC." @default.
• W4297221207 created "2022-09-28" @default.
• W4297221207 creator A5027717516 @default.
• W4297221207 creator A5032760014 @default.
• W4297221207 creator A5050650686 @default.
• W4297221207 creator A5051886871 @default.
• W4297221207 creator A5072508690 @default.
• W4297221207 creator A5083251255 @default.
• W4297221207 date "2022-09-26" @default.
• W4297221207 modified "2023-09-26" @default.
• W4297221207 title "STAC3 determines the slow activation kinetics of Ca_V1.1 currents and inhibits its voltage‐dependent inactivation" @default.
• W4297221207 cites W1628979938 @default.
• W4297221207 cites W1966844362 @default.
• W4297221207 cites W1967299083 @default.
• W4297221207 cites W1991203132 @default.
• W4297221207 cites W1993025208 @default.
• W4297221207 cites W1995610152 @default.
• W4297221207 cites W2008267845 @default.
• W4297221207 cites W2010808385 @default.
• W4297221207 cites W2016547597 @default.
• W4297221207 cites W2019916099 @default.
• W4297221207 cites W2026530002 @default.
• W4297221207 cites W2057724091 @default.
• W4297221207 cites W2059372092 @default.
• W4297221207 cites W2067901022 @default.
• W4297221207 cites W2081714860 @default.
• W4297221207 cites W2087062865 @default.
• W4297221207 cites W2111108423 @default.
• W4297221207 cites W2128578017 @default.
• W4297221207 cites W2130186818 @default.
• W4297221207 cites W2136573755 @default.
• W4297221207 cites W2143459920 @default.
• W4297221207 cites W2145479750 @default.
• W4297221207 cites W2296049218 @default.
• W4297221207 cites W2520207893 @default.
• W4297221207 cites W2558030741 @default.
• W4297221207 cites W2581645585 @default.
• W4297221207 cites W2623805123 @default.
• W4297221207 cites W2751630442 @default.
• W4297221207 cites W2766939625 @default.
• W4297221207 cites W2784802611 @default.
• W4297221207 cites W2810805399 @default.
• W4297221207 cites W2889781306 @default.
• W4297221207 cites W2891793313 @default.
• W4297221207 cites W3032670758 @default.
• W4297221207 doi "https://doi.org/10.1002/jcp.30870" @default.
• W4297221207 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36161458" @default.
• W4297221207 hasPublicationYear "2022" @default.
• W4297221207 type Work @default.
• W4297221207 citedByCount "1" @default.
• W4297221207 countsByYear W42972212072023 @default.
• W4297221207 crossrefType "journal-article" @default.
• W4297221207 hasAuthorship W4297221207A5027717516 @default.
• W4297221207 hasAuthorship W4297221207A5032760014 @default.
• W4297221207 hasAuthorship W4297221207A5050650686 @default.
• W4297221207 hasAuthorship W4297221207A5051886871 @default.
• W4297221207 hasAuthorship W4297221207A5072508690 @default.
• W4297221207 hasAuthorship W4297221207A5083251255 @default.
• W4297221207 hasBestOaLocation W42972212071 @default.
• W4297221207 hasConcept C121332964 @default.
• W4297221207 hasConcept C12554922 @default.
• W4297221207 hasConcept C147944092 @default.
• W4297221207 hasConcept C148898269 @default.
• W4297221207 hasConcept C158617107 @default.
• W4297221207 hasConcept C170493617 @default.
• W4297221207 hasConcept C178790620 @default.
• W4297221207 hasConcept C181911157 @default.
• W4297221207 hasConcept C185592680 @default.
• W4297221207 hasConcept C18699975 @default.
• W4297221207 hasConcept C4141045 @default.
• W4297221207 hasConcept C519063684 @default.
• W4297221207 hasConcept C55493867 @default.
• W4297221207 hasConcept C62520636 @default.
• W4297221207 hasConcept C86803240 @default.
• W4297221207 hasConceptScore W4297221207C121332964 @default.
• W4297221207 hasConceptScore W4297221207C12554922 @default.
• W4297221207 hasConceptScore W4297221207C147944092 @default.
• W4297221207 hasConceptScore W4297221207C148898269 @default.
• W4297221207 hasConceptScore W4297221207C158617107 @default.
• W4297221207 hasConceptScore W4297221207C170493617 @default.
• W4297221207 hasConceptScore W4297221207C178790620 @default.
• W4297221207 hasConceptScore W4297221207C181911157 @default.
• W4297221207 hasConceptScore W4297221207C185592680 @default.
• W4297221207 hasConceptScore W4297221207C18699975 @default.
• W4297221207 hasConceptScore W4297221207C4141045 @default.
• W4297221207 hasConceptScore W4297221207C519063684 @default.
• W4297221207 hasConceptScore W4297221207C55493867 @default.
• W4297221207 hasConceptScore W4297221207C62520636 @default.
• W4297221207 hasConceptScore W4297221207C86803240 @default.
• W4297221207 hasFunder F4320321181 @default.
• W4297221207 hasIssue "11" @default.
• W4297221207 hasLocation W42972212071 @default.
• W4297221207 hasLocation W42972212072 @default.
• W4297221207 hasOpenAccess W4297221207 @default.
• W4297221207 hasPrimaryLocation W42972212071 @default.
• W4297221207 hasRelatedWork W1887884275 @default.
• W4297221207 hasRelatedWork W1967539632 @default.
• W4297221207 hasRelatedWork W1969097312 @default.

• next