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Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d)

C. elegans MEC-4 and UNC-8 belong to the DEG/ENaC family of voltage-independent Na(+) channels and have been implicated in mechanosensation and synaptic remodeling. MEC-4 and UNC-8 hyperactive mutants, designated (d) mutants, conduct enhanced currents and cause cell death due to uncontrolled influx...

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Detalles Bibliográficos
Autores principales: Johnson, Christina K., Miller, David D., Bianchi, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Caltech Library 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223032/
https://www.ncbi.nlm.nih.gov/pubmed/34189421
http://dx.doi.org/10.17912/micropub.biology.000412
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author Johnson, Christina K.
Miller, David D.
Bianchi, Laura
author_facet Johnson, Christina K.
Miller, David D.
Bianchi, Laura
author_sort Johnson, Christina K.
collection PubMed
description C. elegans MEC-4 and UNC-8 belong to the DEG/ENaC family of voltage-independent Na(+) channels and have been implicated in mechanosensation and synaptic remodeling. MEC-4 and UNC-8 hyperactive mutants, designated (d) mutants, conduct enhanced currents and cause cell death due to uncontrolled influx of cations. We show here that MEC-4(d) but not UNC-8(d) currents are further potentiated by treatment with the protease plasmin and that this effect is dependent upon co-expression with the chaperon protein MEC-6. Mammalian DEG/ENaC channels are cleaved by plasmin in the channel finger domain and both MEC-4 and UNC-8 have a predicted plasmin cleavage site in this domain. We previously showed that MEC-4(d), but not UNC-8(d), currents are increased by co-expression with MEC-6, which interacts with the channel via the finger domain. We suggest that interaction of the channel subunit with MEC-6 may render the plasmin cleavage site more accessible. Given that C. elegans expresses a homolog of plasmin, these effects might be relevant in vivo.
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spelling pubmed-82230322021-06-28 Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d) Johnson, Christina K. Miller, David D. Bianchi, Laura MicroPubl Biol New Finding C. elegans MEC-4 and UNC-8 belong to the DEG/ENaC family of voltage-independent Na(+) channels and have been implicated in mechanosensation and synaptic remodeling. MEC-4 and UNC-8 hyperactive mutants, designated (d) mutants, conduct enhanced currents and cause cell death due to uncontrolled influx of cations. We show here that MEC-4(d) but not UNC-8(d) currents are further potentiated by treatment with the protease plasmin and that this effect is dependent upon co-expression with the chaperon protein MEC-6. Mammalian DEG/ENaC channels are cleaved by plasmin in the channel finger domain and both MEC-4 and UNC-8 have a predicted plasmin cleavage site in this domain. We previously showed that MEC-4(d), but not UNC-8(d), currents are increased by co-expression with MEC-6, which interacts with the channel via the finger domain. We suggest that interaction of the channel subunit with MEC-6 may render the plasmin cleavage site more accessible. Given that C. elegans expresses a homolog of plasmin, these effects might be relevant in vivo. Caltech Library 2021-06-21 /pmc/articles/PMC8223032/ /pubmed/34189421 http://dx.doi.org/10.17912/micropub.biology.000412 Text en Copyright: © 2021 by the authors https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle New Finding
Johnson, Christina K.
Miller, David D.
Bianchi, Laura
Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d)
title Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d)
title_full Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d)
title_fullStr Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d)
title_full_unstemmed Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d)
title_short Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d)
title_sort effect of the protease plasmin on c. elegans hyperactive deg/enac channels mec-4(d) and unc-8(d)
topic New Finding
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223032/
https://www.ncbi.nlm.nih.gov/pubmed/34189421
http://dx.doi.org/10.17912/micropub.biology.000412
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