{"id":103277,"date":"2018-03-11T10:25:46","date_gmt":"2018-03-11T10:25:46","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/rastreo-celomico-mediante-genotecas-de-expresion-de-reguladores-de-la-gtpasa-rac1\/"},"modified":"2018-03-11T10:25:46","modified_gmt":"2018-03-11T10:25:46","slug":"rastreo-celomico-mediante-genotecas-de-expresion-de-reguladores-de-la-gtpasa-rac1","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/polipeptidos-y-proteinas\/rastreo-celomico-mediante-genotecas-de-expresion-de-reguladores-de-la-gtpasa-rac1\/","title":{"rendered":"Rastreo cel\u00f3mico mediante genotecas de expresi\u00f3n de reguladores de la gtpasa rac1"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Antonio Castro  Castro <\/strong><\/h2>\n<p>Nuestro objetivo principal era abordar una b\u00fasqueda gen\u00f3mica para identificar nuevas prote\u00ednas implicadas en el mecanismo de translocaci\u00f3n de la gtpasa rac1 a la membrana plasm\u00e1tica. Para realizar el trabajo se eligi\u00f3 un m\u00e9todo de screening por ganancia de funci\u00f3n mediante el que se analizaron 135.000 clones de una genoteca de adnc humana en una l\u00ednea celular reportera hek-293t que expresa de forma estable la versi\u00f3n silvestre de rac1 fusionada a la egfp. Gracias a esta biosonda fluorescente pudimos identificar y aislar aquellos clones cuya sobreexpresi\u00f3n promov\u00eda la translocaci\u00f3n de egfp-rac1 a la membrana. Aislamos un total de 21 clones con capacidad translocadora. Puesto que est\u00e1bamos interesados en descubrir nuevas prote\u00ednas directamente implicadas en el tr\u00e1fico entre citosol y membrana decidimos centrar nuestro trabajo en cuatro prote\u00ednas: dos citos\u00f3licas (coronina-1a y wdr26) y dos transmembrana (basigina y tmem8a). la identificaci\u00f3n de coronina-1a tras nuestro rastreo cel\u00f3mico nos sugiri\u00f3 que esta prote\u00edna, per se o de un modo concertado con el citoesqueleto de f-actina, podr\u00eda estar regulando de forma activa la localizaci\u00f3n en membrana de la gtpasa rac1. La investigaci\u00f3n de esta hip\u00f3tesis nos llev\u00f3 a descubrir un nuevo ciclo de retroalimentaci\u00f3n positiva mediado por coronina-1a y el citoesqueleto de f-actina que contribuye a la amplificaci\u00f3n de la fracci\u00f3n de rac1 activa y unido a la membrana durante procesos de se\u00f1alizaci\u00f3n celular. En este circuito participan otros mediadores de se\u00f1alizaci\u00f3n ya conocidos como arhgef7, pak1, rhogdi y probablemente wdr26. por otra parte, basigina y tmem8a inducen la translocaci\u00f3n de rac1 (adem\u00e1s de otras gtpasas como cdc42 y rhog) de una forma independiente de la ruta anteriormente descrita. Nuestros resultados apuntan a que estas prote\u00ednas transmembrana inducen la estabilizaci\u00f3n y agregaci\u00f3n de balsas lip\u00eddicas en la superficie celular, lo cual supondr\u00eda la acumulaci\u00f3n de rac1 en la membrana.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Rastreo cel\u00f3mico mediante genotecas de expresi\u00f3n de reguladores de la gtpasa rac1<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Rastreo cel\u00f3mico mediante genotecas de expresi\u00f3n de reguladores de la gtpasa rac1 <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Antonio Castro  Castro <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Salamanca<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 23\/07\/2010<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Xose Ramon Garcia Bustelo<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: joaqu\u00edn Teixid\u00f3 calvo <\/li>\n<li>alicia Garcia arroyo (vocal)<\/li>\n<li>neus Agell jane (vocal)<\/li>\n<li>pedro Fern\u00e1ndez salguero (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Antonio Castro Castro Nuestro objetivo principal era abordar una b\u00fasqueda gen\u00f3mica para identificar nuevas prote\u00ednas implicadas en [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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