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Fonctionnalité et dynamique des microvillosités intestinales : rôles clés des protéines de liaison à l'actine

Abstract : Covering the apex of intestinal cells, microvilli are microscopic membrane protrusions structured by a network of actin filaments organized by actin binding proteins. The objective of my thesis consists on investigating how the microvillar actin binding proteins regulate two key features of these organelles: their functionality and plasticity. From a structural point of view, the actin filaments supporting microvilli are tightly packed together by three actin bundling proteins: villin, espin and plastin-1. Using a combined knockout approach, we demonstrate that these three proteins are dispensable to enable and maintain microvilli protrusions. They however confer the appropriate actin organization required for the apical retention of proteins essential for normal intestinal physiology. Besides its structural role, villin also nucleates, caps, and severs actin filaments in a calcium dependent manner, suggesting a central role in microvilli cytoskeleton dynamics. The brush border is indeed subject to major cellular remodeling upon various intestinal stresses (nutrition, pathogen infection, mechanical stress, injury....), which highlights the importance of such cell shape changes. We provide evidences that villin plays a critical role during tissue healing through the initiation of apex disassembly. Such cellular remodeling releases a pool of actin that is remobilized to build efficient migratory structures. Overall, this thesis work documents two important aspects of the epithelial cell biology of the intestine: how the functionality of the apical cellular domain is established and how it can be dynamically remodelled allowing the enterocytes to rapidly respond to a stress.
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Submitted on : Friday, June 21, 2013 - 5:17:55 PM
Last modification on : Tuesday, November 16, 2021 - 4:36:18 AM


  • HAL Id : tel-00836921, version 1


Florent Ubelmann. Fonctionnalité et dynamique des microvillosités intestinales : rôles clés des protéines de liaison à l'actine. Biologie cellulaire. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PAO66649⟩. ⟨tel-00836921⟩



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