Cytoskeletal Transport, Reorganization, and Fusion Regulation in Mast Cell-Stimulus Secretion Coupling.

Gaël Ménasché,Manuela Bratti,Ulrich Blank,Cyril Longé

doi:10.3389/fcell.2021.652077

Abstract

Mast cells are well known for their role in allergies and many chronic inflammatory diseases. They release upon stimulation, e.g., via the IgE receptor, numerous bioactive compounds from cytoplasmic secretory granules. The regulation of granule secretion and its interaction with the cytoskeleton and transport mechanisms has only recently begun to be understood. These studies have provided new insight into the interaction between the secretory machinery and cytoskeletal elements in the regulation of the degranulation process. They suggest a tight coupling of these two systems, implying a series of specific signaling effectors and adaptor molecules. Here we review recent knowledge describing the signaling events regulating cytoskeletal reorganization and secretory granule transport machinery in conjunction with the membrane fusion machinery that occur during mast cell degranulation. The new insight into MC biology offers novel strategies to treat human allergic and inflammatory diseases targeting the late steps that affect harmful release from granular stores leaving regulatory cytokine secretion intact.

Highlights

Mast cells (MC) are granulated cells of the hematopoietic lineage in tissues that localize in large numbers, especially under epithelial and mucosal surfaces exposed to the external environment such as the skin, the airways, and the intestine
The earliest signaling event in response to FcεRI crosslinking is the phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAM) in the cytoplasmic tails of FcεRIβ and disulfide-linked FcεRIγ subunits and the activation of two Srcfamily protein tyrosine kinases (PTK) Fyn and Lyn followed by recruitment of the PTK Syk to the phosphorylated FcεRIγ ITAM (Rivera et al, 2008; Metcalfe et al, 2009)
This study identified the small GTPase, ADP-ribosylation factor 1 (ARF1), as the downstream target of phosphatidyl inositol-3 kinase (PI3K) involved in secretory granules (SG) translocation

Summary

Introduction

Mast cells (MC) are granulated cells of the hematopoietic lineage in tissues that localize in large numbers, especially under epithelial and mucosal surfaces exposed to the external environment such as the skin, the airways, and the intestine. In WASP-deficient BMMC actin polymerization, cell spreading, formation of ruffles, and degranulation was inhibited after FcεRI stimulation (Pivniouk et al, 2003).

Results

Conclusion