Review
Version 1
Preserved in Portico This version is not peer-reviewed
Potential Role of Moesin in Regulating Mast Cell Secretion
Version 1
: Received: 30 June 2023 / Approved: 3 July 2023 / Online: 3 July 2023 (09:55:52 CEST)
A peer-reviewed article of this Preprint also exists.
Theoharides, T.C.; Kempuraj, D. Potential Role of Moesin in Regulating Mast Cell Secretion. Int. J. Mol. Sci. 2023, 24, 12081. Theoharides, T.C.; Kempuraj, D. Potential Role of Moesin in Regulating Mast Cell Secretion. Int. J. Mol. Sci. 2023, 24, 12081.
Abstract
Mast cells play a critical role in allergies and inflammation via secretion of numerous vasoactive, pro-inflammatory and neuro-sensitizing mediators. Secretion may utilize different modes that involve the cytoskeleton, but our understanding of the molecular mechanisms regulating secretion is still not well understood. We previously showed that the ability of the so called mast cell “stabilizer” disodium cromoglycate (cromolyn) to inhibit secretion from rat mast cells closely paralleled the phosphorylation of a 78 kDa protein, and subsequently showed this protein to be moesin, a member of the Ezrin/Radixin/Moesin (ERM) family of proteins, which are involved in linking cell surface-initiated signaling to the actin cytoskeleton. Unlike phosphorylation on the C-terminus Thr558 associated with activation of ERMs, including secretion from macrophages and platelets, we showed that phosphorylation of moesin during inhibition of secretion was on the N-terminal Ser56/74 and Thr66 residues. This phosphorylation pattern could lock moesin in its inactive state and remain inaccessible to bind to the Soluble NSF attachment protein receptors (SNAREs) and synaptosomal associated proteins (SNAPs). Using Confocal microscopic imaging, we showed moesin to colocalize with actin and cluster around secretory granules during inhibition of secretion, In conclusion, the phosphorylation pattern and localization of moesin may be important in the regulation of mast cell secretion and could be targeted for the development of effective inhibitors of secretion from mast cells.
Keywords
ERMs; flavonoids; luteolin; mast cells; mediators; moesin; phosphorylation; secretion; SNAREs; SNAPs; tryptase
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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