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Título: PKCε controls the fusion of secretory vesicles in mast cells in a phosphatidic acid-dependent mode
Fecha de publicación: 18-jun-2021
Editorial: ELSEVIER
Cita bibliográfica: International Journal of Biological Macromolecules, pp 377-389
ISSN: 0141-8130
Palabras clave: PKC
C1 domain
Phosphatidic acid
Resumen: PKCε is highly expressed in mast cells and plays a fundamental role in the antigen-triggered activation of the allergic reaction. Although its regulation by diacylglycerols has been described, its regulation by acidic phospholipids and how this regulation leads to the control of downstream vesicle secretion is barely known. Here, we used structural and evolutionary studies to find the molecular mechanism that explains the selectivity of the C1B domain of PKCε by Phosphatidic Acid (PA). This resided in a collection of Arg residues that form a specific rim on the outer surface of the C1B domain, around the diacylglycerol binding cleft. In RBL-2H3 cells, this basic rim allowed the kinase to respond specifically to phosphatidic acid signals that induced its translocation to the plasma membrane and subsequent activation. Further experiments in cells that overexpress PKCε and a mutant of the PA binding site, showed that PA-dependent PKCε activation increased vesicle degranulation in RBL-2H3 cells, and this correlated with increased SNAP23 phosphorylation. Over-expression of PKCε in these cells also induced an increase in the number of docked vesicles containing SNAP23, when stimulated with PA. This accumulation could be attributed to the stabilizing effect of phosphorylation on the formation of the SNARE complex, which ultimately led to increased release of content in the presence of Ca2+ during the fusion process. Therefore, these findings reinforce the importance of PA signaling in the activation of PKCε, which could be an important target to inhibit the exacerbated responses of these cells in the allergic reaction.
Autor/es principal/es: Serrano-Lopez, Emilio M.
Lopez-Martínez, David
Gomez-Fernandez, Juan C.
Corbalan-García, Senena
Facultad/Departamentos/Servicios: Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular A
URI: http://hdl.handle.net/10201/125827
DOI: https://doi.org/10.1016/j.ijbiomac.2021.06.019
Tipo de documento: info:eu-repo/semantics/article
Número páginas / Extensión: 13
Derechos: info:eu-repo/semantics/openAccess
Descripción: ©2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Acepted Manuscript version of a Published Work that appeared in final form in International Journal of Biological Macromolecules To access the final edited and published work see https://doi.org/10.1016/j.ijbiomac.2021.06.019
Aparece en las colecciones:Artículos: Bioquímica y Biología Molecular "A"

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