{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:35:46Z","timestamp":1791275746634,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,2]],"date-time":"2013-01-02T00:00:00Z","timestamp":1357084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:p>\n                    Mediator release from mast cells is a critical step in allergic and inflammatory disease. However, the processes regulating the latter stages of granule release are yet to be fully understood. Rab27 small\n                    <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>\n                    ases regulate release of secretory lysosomes in a variety of cells, including mast cell granules. In the present study, using murine bone marrow\u2010derived mast cells (\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    ) from Rab27\u2010deficient mutant mice, we found that, in contrast to Rab27b, Rab27a primarily plays an inhibitory role in regulating degranulation. Immunofluorescence analysis revealed that resting Rab27a\u2010deficient (\n                    <jats:italic>ashen<\/jats:italic>\n                    )\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    s display abnormal cortical F\u2010actin distribution. Actin disassembly prior to IgE cross\u2010linking increased wild\u2010type\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    secretion to\n                    <jats:italic>ashen<\/jats:italic>\n                    levels, suggesting that changes in the integrity of cortical F\u2010actin underlie the\n                    <jats:italic>ashen<\/jats:italic>\n                    phenotype. Comparison of the secretory impairment of\n                    <jats:italic>Rab27b<\/jats:italic>\n                    knockout and\n                    <jats:italic>Rab27a<\/jats:italic>\n                    \/\n                    <jats:italic>b<\/jats:italic>\n                    double knockout\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    s highlighted a secondary positive role for Rab27a in enhancing degranulation. Rab27 is known to interact with actin via its effectors melanophilin (Mlph) and myosin\u00a0Va (MyoVa) in other cell types. To better understand the differing roles of Rab27 proteins, we analysed the secretory phenotype of\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    s derived from mice lacking Rab27 effector proteins. These experiments revealed that the phenotype of\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    s deficient in Mlph (\n                    <jats:italic>leaden<\/jats:italic>\n                    ) and\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    s deficient in MyoVa (\n                    <jats:italic>dilute<\/jats:italic>\n                    ) resembles the hyper\u2010secretion of\n                    <jats:italic>ashen<\/jats:italic>\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    s, while Munc13\u20104\u2010deficient (\n                    <jats:italic>jinx<\/jats:italic>\n                    )\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    s phenocopy the\n                    <jats:italic>Rab27b<\/jats:italic>\n                    knockout and double\n                    <jats:italic>Rab27a<\/jats:italic>\n                    \/\n                    <jats:italic>b<\/jats:italic>\n                    knockout secretory impairment. We conclude that Rab27a and Rab27b regulate distinct steps in the\n                    <jats:styled-content style=\"fixed-case\">BMMC<\/jats:styled-content>\n                    degranulation pathway, with Rab27a\/Mlph\/MyoVa regulating cortical actin stability upstream of Rab27a\/b\/Munc13\u20104\u2010dependent granule exocytosis.\n                  <\/jats:p>","DOI":"10.1111\/febs.12081","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T09:52:41Z","timestamp":1354182761000},"page":"892-903","source":"Crossref","is-referenced-by-count":72,"title":["Distinct and opposing roles for\n                    <scp>R<\/scp>\n                    ab27a\/\n                    <scp>M<\/scp>\n                    lph\/\n                    <scp>M<\/scp>\n                    yo\n                    <scp>V<\/scp>\n                    a and\n                    <scp>R<\/scp>\n                    ab27b\/\n                    <scp>M<\/scp>\n                    unc13\u20104 in mast cell secretion"],"prefix":"10.1111","volume":"280","author":[{"given":"Rajesh K.","family":"Singh","sequence":"first","affiliation":[{"name":"Molecular Medicine, National Heart and Lung Institute Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Molecular Medicine, National Heart and Lung Institute Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wasmeier","sequence":"additional","affiliation":[{"name":"Molecular Medicine, National Heart and Lung Institute Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silene T.","family":"Wavre\u2010Shapton","sequence":"additional","affiliation":[{"name":"Molecular Medicine, National Heart and Lung Institute Imperial College London UK"},{"name":"Institute of Ophthalmology University College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Recchi","sequence":"additional","affiliation":[{"name":"Molecular Medicine, National Heart and Lung Institute Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio D.","family":"Catz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine The Scripps Research Institute La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Futter","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology University College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Tolmachova","sequence":"additional","affiliation":[{"name":"Molecular Medicine, National Heart and Lung Institute Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair 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