Modulation der β1-Integrin-Lokalisation an der apikalen Plasmamembran durch Galektin-3

Epithelien bilden das Deck- und Abschlussgewebe aller äußerer und innerer Oberflächen von mehrzelligen Organismen. Epithelzellen zeichnen sich durch ihren polaren Aufbau und ihre morphologisch und funktionell zu unterscheidende apikale und basolaterale Membrandomänen aus. Um dies zu gewährleisten, b...

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Bibliographische Detailangaben
1. Verfasser: Hönig, Ellena
Beteiligte: Jacob, Ralf (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Deutsch
Veröffentlicht: Philipps-Universität Marburg 2017
Medizin
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Inhaltsangabe: Epithelia line the outer and inner surfaces of multicellular organisms. Epithelial cells are characterized by their polar structure and their morphologically and functionally distinct apical and basolateral membrane domains. To establish and maintain their polarity, epithelial cells possess a specific transport machinery that ensures directional transport to the respective membrane domains. An important sorting receptor in apical protein transport is galectin-3. This soluble lectin is synthesized in the cytosol and secreted in polarized MDCK cells preferentially at the apical membrane. Here, it enters the endosomal compartment via endocytosis and assists in the sorting of newly synthesized apical glycoproteins. While binding of galectin-3 can occur at both plasma membrane domains, clustering and endocytosis of the lectin were observed exclusively at the apical domain. Integrins were identified as interaction partners of galectin-3 at the apical plasma membrane of MDCK cells by mass spectrometry. This interesting observation raised the question whether galectin-3 is involved in the apical localization of integrins in epithelial cells. To test this, the surface distibution of the most widespread family member, β1-integrin was analysed in galcetin-3 overexpressing and galectin-3 depleted MDCK cells by biochemical assays and fluorescence microscopy. In galectin-3 overexpressing cells as well as in the presence of exogenous, recombinant galectin-3 the apical localization of β1-integrin was enhanced. Conversely, depletion of the lectin decreased apical expression leves of β1-integrin. Moreover, inhibition of galectin-3 endocytosis had the same effect. Using metabolic labeling and transport experiments it was shown, that galectin-3 mediates sorting of newly synthesized β1-integrin in the apical transport pathway. This study shows for the first time, that galectin-3 is able to modulate the surface distribution of the integrin family member β1-integrin in polarized epithelial cells.