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Metabolic control of cell adhesion and migration through beta1A integrin acetylation : be aware of the acetylation switch!

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Defense Thèse de doctorat : Univ. Genève, 2015 - Sc. 4875 - 2015/12/08
Abstract Alpha5beta1A integrins form two types of cell-matrix adhesions with differential functions: short, peripherally located focal adhesions (FAs) that provide strong anchorage to the substrate and intracellular signalling; and long, centrally located fibrillar adhesions (FBs) that enable the formation of fibronectin (FN) fibrils in the pericellular space. Despite the critical role of alpha5beta1A integrins for FN deposition during fibrosis, the integrins’ relevant signalling is not well understood. Interestingly, beta1A integrin bears a lysine acetylation site located within integrin’s kindlin recognition sequence in the cytoplasmic tail. Genetic deletion of kindlin has been demonstrated to handicap cell spreading and the formation of thin, centrally located FBs. These facts suggest a functional link between integrin acetylation, kindlin binding affinities, FB formation and FN fibrillogenesis capacities. Therefore, we hypothesized that acetylation of beta1A integrin might function as regulatory switch which defines for each beta1A integrin its FA or FB character.
Keywords Beta1A integrinAcetylationFibronectinFibrillogenesisMuscleMyopathyMuscular dystrophyCell signallingCell adhesionFibrillar adhesionFocal adhesionExtracellular matrixBeta1D integrinFibrosisAcetyl-Coenzyme AMetabolismAcetyl-tubulinLysine deacetylaseAcetyltransferaseCell migrationCell morphology
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URN: urn:nbn:ch:unige-801528
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Thesis (24.2 MB) - public document Free access
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Research group Migration cellulaire (645)
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KASTBERGER, Birgit. Metabolic control of cell adhesion and migration through beta1A integrin acetylation : be aware of the acetylation switch!. Université de Genève. Thèse, 2015. https://archive-ouverte.unige.ch/unige:80152

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Deposited on : 2016-02-01

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