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Intracellular membrane trafficking of E-cadherin in Drosophila

Tanasic, Dajana

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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.

Document type: Dissertation
Supervisor: Riechmann, PD Dr. Veit
Place of Publication: Heidelberg
Date of thesis defense: 1 July 2022
Date Deposited: 06 Jul 2022 07:02
Date: 2022
Faculties / Institutes: The Faculty of Bio Sciences > Institute of Pharmacy and Molecular Biotechnology
Medizinische Fakultät Heidelberg
Medizinische Fakultät Mannheim > Zentrum für Medizinische Forschung
Medizinische Fakultät Mannheim > Zentrum für Biomedizin und Medizintechnik (CBTM)
Medizinische Fakultät Mannheim > Mannheimer Institute of Public Health (MIPH)
DDC-classification: 570 Life sciences
Controlled Keywords: Drosophila, E-cadherin, Trafficking
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