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Abstract
The maintenance of the cell-cell adhesion is crucial for tissue integrity and epithelial homeostasis. E-cadherin is the main building block of the cell junctions called adherens junctions. Disruption in E-cadherin secretion to the plasma membrane causes tissue disintegration and metastasis. Despite the importance of the proper E-cadherin delivery to the plasma membrane, the mechanisms of transport remain unknown. Here, I investigate E-cadherin trafficking using the follicular epithelium of Drosophila ovaries. I show that the newly synthesized and endocytosed Drosophila E-cadherin (DE-cadherin) transverses through the apical Rab7 and Rab11 endosomal compartments. The signals for the proper DE-cadherin delivery to apical endosomes are located within the protein`s cytoplasmic tail. Furthermore, the Rab7 recruits a sorting nexin 16 (Snx16) for subsequent DE-cadherin transport. Snx16 delivers DE-cadherin to the Rab11 compartment via the tubulation activity. My finding suggests that Snx16 is also required for the stabilization of the DE-cadherin and Armadillo complex, which is necessary for efficient DE-cadherin trafficking. Further, the exocyst component Sec15 and the motor MyosinV (MyoV) are then recruited by Rab11. This results in the formation of the MyoV/Sec15/Rab11 complex that uses apical actin tracks to transport DE-cadherin to the zonula adherens, where it creates a continuous adhesion belt. My data shows that equivalent levels of MyoV, Rab11 and Sec15 are required for the proper MyoV/Sec15/Rab11 complex formation and unhampered DE-cadherin delivery to the plasma membrane. Upon the expression of the nonfunctional MyoV, DE-cadherin accumulates in Rab7 and Rab11 endosomal compartments, and zonula adherens cannot be continuously formed. Additionally, my data reveal that the DE-cadherin is also transported along basal actin cables via the MyoV/Sec15/Rab11 complex for delivery to the basolateral plasma membrane. Taken together, my findings shed light on the DE-cadherin secretion pathways. I was able to show several additional aspects of E-cadherin transport within endosomal compartments and towards the plasma membrane. As a result, my data contribute to a better understanding of epithelial homeostasis and the prevention of diseases and their consequences, including cancer metastasis.
Dokumententyp: | Dissertation |
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Erstgutachter: | Riechmann, PD Dr. Veit |
Ort der Veröffentlichung: | Heidelberg |
Tag der Prüfung: | 1 Juli 2022 |
Erstellungsdatum: | 06 Jul. 2022 07:02 |
Erscheinungsjahr: | 2022 |
Institute/Einrichtungen: | Fakultät für Ingenieurwissenschaften > Institut für Pharmazie und molekulare Biotechnologie
?? i-50000 ?? Medizinische Fakultät Mannheim > Zentrum für Medizinische Forschung Medizinische Fakultät Mannheim > Zentrum für Biomedizin und Medizintechnik (CBTM) Medizinische Fakultät Mannheim > Zentrum für Präventivmedizin und Digitale Gesundheit Baden-Württemberg |
DDC-Sachgruppe: | 570 Biowissenschaften, Biologie |
Normierte Schlagwörter: | Drosophila, E-cadherin, Trafficking |