SNARE complex‐mediated degranulation in mast cells

Abstract

Mast cell function and dysregulation is important in the development and progression of allergic and autoimmune disease. Identifying novel proteins involved in mast cell function and disease progression is the first step in the design of new therapeutic strategies. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a family of proteins demonstrated to mediate the transport and fusion of secretory vesicles to the membrane in mast cells, leading to the subsequent release of the vesicle cargo through an exocytotic mechanism. The functional role[s] of specific SNARE family member complexes in mast cell degranulation has not been fully elucidated. Here, we review recent and historical data on the expression, formation and localization of various SNARE proteins and their complexes in murine and human mast cells. We summarize the functional data identifying the key SNARE family members that appear to participate in mast cell degranulation. Furthermore, we discuss the utilization of RNA interference (RNAi) methods to validate SNARE function and the use of siRNA as a therapeutic approach to the treatment of inflammatory disease. These studies provide an overview of the specific SNARE proteins and complexes that serve as novel targets for the development of new therapies to treat allergic and autoimmune disease.

RBL cells as models for in vitro studies of mast cells and basophils

“…In support of this notion are the reports that demonstrated the involvement of same SNARE proteins in mediating the fusion events that lead to degranulation in either cell type. Immunohistochemistry studies have further supported these studies by demonstrating similar cellular locations of the SNARE proteins in primary MCs and RBL cells, whereby SNAP23 and syntaxin 4 localize to the plasma membrane and syntaxin 3 and VAMP‐2, −3, −7, and −8 primarily localize to the SGs (reviewed in). Furthermore, similar protein interactions between SNARE proteins were noted in the primary MCs and the RBL cells, demonstrating protein complexes consisting of SNAP‐23, Syntaxin 4 and VAMP‐2, VAMP‐8, VAMP‐7, and VAMP‐3 (reviewed in).…”

Intracellular trafficking and secretion of inflammatory cytokines

“…A large number of SNARE proteins and complexes have been identified in mast cells (summarized in [97]), although in many cases the precise membrane fusion step that each mediates is not known. VAMP8 can control various stages of granule-mediated secretion.…”

Decoding the Regulation of Mast Cell Exocytosis by Networks of Rab GTPases

“…In addition, the lysosomal nature of the mast cell SGs raises questions as to how are secretory lysosomes formed and how do they acquire their exocytosis competence. Consistent with the complexity of mast cell exocytosis, multiple SNARE proteins have been implicated in controlling this process (11,(16)(17)(18).…”