title: Characterization of mast cell secretory granules and their cell biology.
abstract: Exocytosis and secretion of secretory granule (SG) contained inflammatory mediators is the primary mechanism by which mast cells exert their protective immune responses in host defense, as well as their pathological functions in allergic reactions and anaphylaxis. Despite their central role in mast cell function, the molecular mechanisms underlying the biogenesis and secretion of mast cell SGs remain largely unresolved. Early studies have established the lysosomal nature of the mast cell SGs and implicated SG homotypic fusion as an important step occurring during both their biogenesis and compound secretion. However, the molecular mechanisms that account for key features of this process largely remain to be defined. A novel high-resolution imaging based methodology allowed us to screen Rab GTPases for their phenotypic and functional impact and identify Rab networks that regulate mast cell secretion. This screen has identified Rab5 as a novel regulator of homotypic fusion of the mast cell SGs that thereby regulates their size and cargo composition.
authors.affiliation: 1 Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .
authors.forename: Nurit Pereg
authors.initials: NP
authors.lastname: Azouz
authors.forename: Ilan
authors.initials: I
authors.lastname: Hammel
authors.forename: Ronit
authors.initials: R
authors.lastname: Sagi-Eisenberg
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D005089:Exocytosis; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D008247:Lysosomes; D008407:Mast Cells / Q000276:immunology* / Q000648:ultrastructure; D008561:Membrane Fusion; D022142:Secretory Vesicles / Q000502:physiology*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D020696:rab5 GTP-Binding Proteins