{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T15:59:51Z","timestamp":1771948791134,"version":"3.50.1"},"reference-count":34,"publisher":"Proceedings of the National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,4,3]]},"abstract":"<jats:p>\n            The Rab27 GTPase subfamily consists of two closely related homologs, Rab27a and Rab27b. Rab27a has been shown previously to regulate organelle movement and regulated exocytosis in a wide variety of secretory cells. However, the role of the more restrictedly expressed Rab27b remains unclear. Here we describe the creation of\n            <jats:italic>Rab27b<\/jats:italic>\n            knockout (KO) strain that was subsequently crossed with the naturally occurring\n            <jats:italic>Rab27a<\/jats:italic>\n            KO line,\n            <jats:italic>ashen<\/jats:italic>\n            , to produce double KO (\n            <jats:italic>Rab27a<\/jats:italic>\n            <jats:sup>ash\/ash<\/jats:sup>\n            <jats:italic>Rab27b<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) mice.\n            <jats:italic>Rab27b<\/jats:italic>\n            KO (and double KO) exhibit significant hemorrhagic disease in contrast to\n            <jats:italic>ashen<\/jats:italic>\n            mice.\n            <jats:italic>In vitro<\/jats:italic>\n            assays demonstrated impaired aggregation with collagen and U46619 and reduced secretion of dense granules in both\n            <jats:italic>Rab27b<\/jats:italic>\n            and double KO strains. Additionally, we detected a 50% reduction in the number of dense granules per platelet and diminished platelet serotonin content, possibly due to a dense granule packaging defect into proplatelets during megakaryocyte maturation. The presence of Rab27a partially compensated for the secretory defect but not the reduced granule number. The morphology and function of platelet \u03b1-granules were unaffected. Our data suggest that Rab27b is a key regulator of dense granule secretion in platelets and thus a candidate gene for \u03b4-storage pool deficiency in humans.\n          <\/jats:p>","DOI":"10.1073\/pnas.0609879104","type":"journal-article","created":{"date-parts":[[2007,3,24]],"date-time":"2007-03-24T00:38:21Z","timestamp":1174696701000},"page":"5872-5877","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":163,"title":["Rab27b regulates number and secretion of platelet dense granules"],"prefix":"10.1073","volume":"104","author":[{"given":"Tanya","family":"Tolmachova","sequence":"first","affiliation":[{"name":"*Molecular and Cellular Medicine, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom;"}]},{"given":"Magnus","family":"\u212bbrink","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Uppsala University, 751 05 Uppsala, Sweden;"}]},{"given":"Clare E.","family":"Futter","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom; and"}]},{"given":"Kalwant S.","family":"Authi","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, King's College London, London SE1 9NH, United Kingdom"}]},{"given":"Miguel C.","family":"Seabra","sequence":"additional","affiliation":[{"name":"*Molecular and Cellular Medicine, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom;"}]}],"member":"341","published-online":{"date-parts":[[2007,4,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35057024"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5072"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601617103"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R500003200"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35052055"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvi002"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1247\/csf.28.465"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9219.2004.00190.x"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/76024"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(01)02227-4"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140212797"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-07-0452"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2004.09.007"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215058"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.08.212"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2436350100"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.5.8823"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)71450-6"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0977"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90531-6"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008868325009"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-040196"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.10.2626.2626"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00651-7"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309426200"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00855-9"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.041863"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20986"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306960200"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200606050"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.147.6.1299"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002834200"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-835674"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1976.tb07452.x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0609879104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T19:33:32Z","timestamp":1649792012000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0609879104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,3]]},"references-count":34,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2007,4,3]]}},"alternative-id":["10.1073\/pnas.0609879104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0609879104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,3]]},"assertion":[{"value":"2006-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}