{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T21:05:11Z","timestamp":1777064711038,"version":"3.51.4"},"reference-count":28,"publisher":"Proceedings of the National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,8,25]]},"abstract":"<jats:p>\n            Membrane traffic along the endocytic and exocytic pathways relies on the appropriate localization and activation of a series of different Rab GTPases. Rabs are activated by specific guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs). GEF cascades, in which one Rab in its GTP-bound form recruits the GEF that activates the next Rab along the pathway, can account for the sequential activation of a series of Rabs, but it does not explain how the first Rab is inactivated after the next Rab has been activated. We present evidence for a counter-current GAP cascade that serves to restrict the spatial and temporal overlap of 2 Rabs, Ypt1p and Ypt32p, on the exocytic pathway in\n            <jats:named-content content-type=\"genus-species\">Saccharomyces cerevisiae<\/jats:named-content>\n            . We show that Gyp1p, a GAP for Ypt1p, specifically interacts with Ypt32p, and that this interaction is important for the localization and stability of Gyp1p. Moreover, we demonstrate that, in WT cells, Ypt1p compartments are converted over time into Ypt32p compartments, whereas in\n            <jats:italic>gyp1<\/jats:italic>\n            \u0394 cells there is a significant increase in compartments containing both proteins that reflects a slower transition from Ypt1p to Ypt32p. GEF cascades working in concert with counter-current GAP cascades could generate a programmed series of Rab conversions responsible for regulating the choreography of membrane traffic.\n          <\/jats:p>","DOI":"10.1073\/pnas.0906536106","type":"journal-article","created":{"date-parts":[[2009,8,5]],"date-time":"2009-08-05T01:44:00Z","timestamp":1249436640000},"page":"14408-14413","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":157,"title":["A Rab GAP cascade defines the boundary between two Rab GTPases on the secretory pathway"],"prefix":"10.1073","volume":"106","author":[{"given":"F\u00e9lix E.","family":"Rivera-Molina","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520; and"}]},{"given":"Peter J.","family":"Novick","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093"}]}],"member":"341","published-online":{"date-parts":[[2009,8,25]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601617103"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02147-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1500"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35052055"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200201003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.043"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01037.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02405-05"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.3.563"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.131.3.583"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.3.1015"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.5.1215"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.01-07-0365"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.9.3815-3826.2004"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04847"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.6.3253"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.19.5216"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-03-0258"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-11-0707"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04717"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04737"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200111081"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205783200"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2000.059"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200302038"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.014225"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.12.4149"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.103.038422"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0906536106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T21:14:14Z","timestamp":1653340454000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0906536106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,25]]},"references-count":28,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2009,8,25]]}},"alternative-id":["10.1073\/pnas.0906536106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0906536106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,25]]},"assertion":[{"value":"2009-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-08-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}