title: Rab27b regulates mast cell granule dynamics and secretion.
abstract: The Rab GTPase family regulates membrane domain organization and vesicular transport pathways. Recent studies indicate that one member of the family, Rab27a, regulates transport of lysosome-related organelles in specialized cells, such as melanosomes and lytic granules. Very little is known about the related isoform, Rab27b. Here we used genetically modified mice to study the involvement of the Rab27 proteins in mast cells, which play key roles in allergic responses. Both Rab27a and Rab27b isoforms are expressed in bone marrow-derived mast cells (BMMC) and localize to secretory granules. Nevertheless, secretory defects as measured by beta-hexosaminidase release in vitro and passive cutaneous anaphylaxis in vivo were found only in Rab27b and double Rab27 knockout (KO) mice. Immunofluorescence studies suggest that a subset of Rab27b and double Rab27-deficient BMMCs exhibit mild clustering of granules. Quantitative analysis of live-cell time-lapse imaging revealed that BMMCs derived from double Rab27 KO mice showed almost 10-fold increase in granules exhibiting fast movement (>1.5 microm/s), which could be disrupted by nocodazole. These results suggest that Rab27 proteins, particularly Rab27b, play a crucial role in mast cell degranulation and that their action regulates the transition from microtubule to actin-based motility.
authors.affiliation: Molecular and Cellular Medicine, National Heart and Lung Institute, Imperial College London SW7 2AZ, UK.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Mizuno
authors.forename: Tanya
authors.initials: T
authors.lastname: Tolmachova
authors.forename: Dmitry S
authors.initials: DS
authors.lastname: Ushakov
authors.forename: Maryse
authors.initials: M
authors.lastname: Romao
authors.forename: Magnus
authors.initials: M
authors.lastname: Abrink
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ferenczi
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001854:Bone Marrow Cells / Q000378:metabolism*; D002478:Cells, Cultured; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms; D022142:Secretory Vesicles / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D000199:Actins; D020033:Protein Isoforms; C512958:Rab27b protein, mouse; D020691:rab GTP-Binding Proteins