αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors

Proalgesic sensitization of peripheral nociceptors in painful syn-dromes is a complex molecular process poorly understood thatinvolves mobilization of thermosensory receptors to the neuronalsurface. However, whether recruitment of vesicular thermoTRPchannels is a general mechanism underlying sensiti...

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Autores: Devesa Giner, Isabel, Ferrándiz-Huertas, Clotilde, Mathivanan, Sakthikumar, Ferrer-Montiel, Antonio
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Miguel Hernández de Elche
Repositorio:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/35281
Acceso en línea:https://hdl.handle.net/11000/35281
Access Level:acceso abierto
Palabra clave:CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica
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spelling αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptorsDevesa Giner, IsabelFerrándiz-Huertas, ClotildeMathivanan, SakthikumarFerrer-Montiel, AntonioCDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. BiofísicaProalgesic sensitization of peripheral nociceptors in painful syn-dromes is a complex molecular process poorly understood thatinvolves mobilization of thermosensory receptors to the neuronalsurface. However, whether recruitment of vesicular thermoTRPchannels is a general mechanism underlying sensitization of allnociceptor types or is subtype-specific remains controversial. Wereport that sensitization-induced Ca2+-dependent exocytotic inser-tion of transient receptor potential vanilloid 1 (TRPV1) receptors tothe neuronal plasma membrane is a mechanism specifically usedby peptidergic nociceptors to potentiate their excitability. Notably,we found that TRPV1 is present in large dense-core vesicles(LDCVs) that were mobilized to the neuronal surface in responseto a sensitizing insult. Deletion or silencing of calcitonin-gene–related peptide alpha (αCGRP) gene expression drastically reducedproalgesic TRPV1 potentiation in peptidergic nociceptors by abro-gating its Ca2+-dependent exocytotic recruitment. These findingsuncover a context-dependent molecular mechanism of TRPV1 alge-sic sensitization and a previously unrecognized role of αCGRP inLDCV mobilization in peptidergic nociceptors. Furthermore, theseresults imply that concurrent secretion of neuropeptides and chan-nels in peptidergic C-type nociceptors facilitates a rapid modula-tion of pain signalingDepartamentos de la UMH::Bioquímica y Biología Molecular202520252014info:eu-repo/semantics/articleapplication/pdf6application/pdfhttps://hdl.handle.net/11000/35281reponame:REDIUMH. Depósito Digital de la UMHinstname:Universidad Miguel Hernández de ElcheIngléshttps://doi.org/10.1073/pnas.142025211info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:dspace.umh.es:11000/352812026-05-27T13:36:21Z
dc.title.none.fl_str_mv αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
title αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
spellingShingle αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
Devesa Giner, Isabel
CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica
title_short αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
title_full αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
title_fullStr αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
title_full_unstemmed αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
title_sort αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
dc.creator.none.fl_str_mv Devesa Giner, Isabel
Ferrándiz-Huertas, Clotilde
Mathivanan, Sakthikumar
Ferrer-Montiel, Antonio
author Devesa Giner, Isabel
author_facet Devesa Giner, Isabel
Ferrándiz-Huertas, Clotilde
Mathivanan, Sakthikumar
Ferrer-Montiel, Antonio
author_role author
author2 Ferrándiz-Huertas, Clotilde
Mathivanan, Sakthikumar
Ferrer-Montiel, Antonio
author2_role author
author
author
dc.contributor.none.fl_str_mv Departamentos de la UMH::Bioquímica y Biología Molecular
dc.subject.none.fl_str_mv CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica
topic CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica
description Proalgesic sensitization of peripheral nociceptors in painful syn-dromes is a complex molecular process poorly understood thatinvolves mobilization of thermosensory receptors to the neuronalsurface. However, whether recruitment of vesicular thermoTRPchannels is a general mechanism underlying sensitization of allnociceptor types or is subtype-specific remains controversial. Wereport that sensitization-induced Ca2+-dependent exocytotic inser-tion of transient receptor potential vanilloid 1 (TRPV1) receptors tothe neuronal plasma membrane is a mechanism specifically usedby peptidergic nociceptors to potentiate their excitability. Notably,we found that TRPV1 is present in large dense-core vesicles(LDCVs) that were mobilized to the neuronal surface in responseto a sensitizing insult. Deletion or silencing of calcitonin-gene–related peptide alpha (αCGRP) gene expression drastically reducedproalgesic TRPV1 potentiation in peptidergic nociceptors by abro-gating its Ca2+-dependent exocytotic recruitment. These findingsuncover a context-dependent molecular mechanism of TRPV1 alge-sic sensitization and a previously unrecognized role of αCGRP inLDCV mobilization in peptidergic nociceptors. Furthermore, theseresults imply that concurrent secretion of neuropeptides and chan-nels in peptidergic C-type nociceptors facilitates a rapid modula-tion of pain signaling
publishDate 2014
dc.date.none.fl_str_mv 2014
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/11000/35281
url https://hdl.handle.net/11000/35281
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1073/pnas.142025211
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
6
application/pdf
dc.source.none.fl_str_mv reponame:REDIUMH. Depósito Digital de la UMH
instname:Universidad Miguel Hernández de Elche
instname_str Universidad Miguel Hernández de Elche
reponame_str REDIUMH. Depósito Digital de la UMH
collection REDIUMH. Depósito Digital de la UMH
repository.name.fl_str_mv
repository.mail.fl_str_mv
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