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35E1-48A3-A1ce-0C960f5dd165.Txt Dépôt Institutionnel de l’Université libre de Bruxelles / Université libre de Bruxelles Institutional Repository Thèse de doctorat/ PhD Thesis Citation APA: Moes, M. (2007). Interaction of the cytoskeletal protein talin with the integrin beta3 subunit cytoplasmic tail: characterization of the talin rod IBS2 integrin binding site (Unpublished doctoral dissertation). Université libre de Bruxelles, Faculté des Sciences – Sciences biologiques, Bruxelles. Disponible à / Available at permalink : https://dipot.ulb.ac.be/dspace/bitstream/2013/210658/6/8507e4dc-35e1-48a3-a1ce-0c960f5dd165.txt (English version below) Cette thèse de doctorat a été numérisée par l’Université libre de Bruxelles. L’auteur qui s’opposerait à sa mise en ligne dans DI-fusion est invité à prendre contact avec l’Université ([email protected]). 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Toute autre utilisation non mentionnée ci-dessus nécessite l’autorisation de l’auteur de l’œuvre ou de l’ayant droit. ------------------------------------------------------ English Version ------------------------------------------------------------------- This Ph.D. thesis has been digitized by Université libre de Bruxelles. The author who would disagree on its online availability in DI-fusion is invited to contact the University ([email protected]). If a native electronic version of the thesis exists, the University can guarantee neither that the present digitized version is identical to the native electronic version, nor that it is the definitive official version of the thesis. DI-fusion is the Institutional Repository of Université libre de Bruxelles; it collects the research output of the University, available on open access as much as possible. The works included in DI-fusion are protected by the Belgian legislation relating to authors’ rights and neighbouring rights. 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D 03517 UNIVERSITÉ LIBRE DE BRUXELLES Faculté des Sciences - Biologie Moléculaire Centre de Biologie Structurale et Bioinformatique Interaction of the cytoskeletal protein talin with the integrin P3 subunit cytoplasmic tail: Characterization of the talin rod IBS2 integrin binding site. Thèse présentée en vue de l’obtention du grade de Docteur en Sciences par Moes Michèle Promoteur : M. Eric Goormaghtigh, Professeur, Université Libre de Bruxelles Co-promoteur : Mme Nelly Kieffer, Professeur, Université du Luxembourg Octobre 2007 Université Libre de Bruxelles 0033S213S Je voudrais exprimer ma profonde reconnaissance à mon promoteur ^Monsieur Ce (Docteur ‘Eric Çoormagfitipfi. Merci pour votre disponiôiCité inconditionneCCe et merci pour Ca confiance que vous m'avez témoignée. Je suis tout particuCièrement reconnaissante envers mon co-promoteur Madame Ce (professeur JfeCCy %ieffer qui m ’a cfiaCeureusement accueiCCie dans son équipe de recHercHe et qui m’a soutenue tout au Cong de ces années de travaiC. J'ejçprime ma profonde gratitude à Monsieur (e Docteur Eaôrice JfomSCé et à Monsieur Ce Docteur MicHeC Vanden6randen qui ont Sien vouCu juger ce travaiC en tant que rapporteurs. Je Ces remercie vivement pour Cintérêt qu’iCs ont porté à ce travaiC Je souCiaite sincèrement remercier Monsieur Ce Docteur David CritcRCey pour sa coCCaSoration scientifique et pour son accueiC à Leicester. J’adresse mes remerciements au Ministère de Ca CuCture, de CEnseignement Supérieur et de Ca (RecHercCie pour son soutien financier sans CequeC ce travaiC n’aurait jamais vu Ce jour, ainsi qu ’au Eonds JVationaC de Ca (RecSercSe du LuyemSourg pour son soutien financier pour Cimpression du manuscrit. Je tiens égaCement à remercier très cCiaCeureusement Ces memSres du £(B(PI qui ont travaiCCé à mes côtés, et qui ont su me conseiCCer, m’aider et m’encourager pendant tout ce temps: ECisaBetC, jACexgndre, Martine, Sophie, (Patrie^ Christine, Sandra, EaSrice, Laurent, Sébastien, ChantaCet Stéphanie. Je souhaite finalement remercier de tout mon coeur mon père, Michelle, SyCvie, (Raymonde et Eom, qui ont su me soutenir et me réconforter auy^ moments diffeiCes pendant ces dernières années. TABLE OF CONTENTS TABLE OF CONTENTS................................................................................................................................1 PUBLICA TION AND LIST OF COMMUNICA TIONS...................................................................................7 SUMMARY OF TABLES AND FIGURES...................................................................................................... 9 ABBREVIATIONS....................................................................................................................................... 13 INTRODUCTION......................................................................................................................................... 15 CHAPTER I: The Integrin Gene Family...................................................................................................... 17 A. Introduction.......................................................................................................................................... 17 B. The integrin gene family......................................................................................................................21 B. 1. The integrin a subunits.................................................................................................................. 23 B. 2. The integrin j3 subunits................................................................................................................... 25 C. Structural organization of integrins.................................................................................................... 27 C. I. The extracellular N-terminal ligand binding domain...................................................................... 27 C. 2. The extracellular and transmembrane stalk région......................................................................... 29 C. 3. The integrin cytoplasmic domains.................................................................................................. 31 D. Integrin function.................................................................................................................................. 35 D. l. Integrin inside-out signalling.........................................................................................................37 D. 2. Integrin outside-in signalling......................................................................................................... 39 E. The integrin cytoplasmic tails regulate integrin signalling..................................................................39 F. The integrin-cytoskeleton link: focal adhesions.................................................................................. 41 G. Particular features of the platelet-specifïc integrin allbp3.................................................................45 Chapter II: The cytoskeletal protein talin....................................................................................................49 A. Introduction..........................................................................................................................................49 B. Talin gene duplication during évolution............................................................................................. 51 C. Structural and functional organization of talin...................................................................................53
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