eprintid: 31866
rev_number: 19
eprint_status: archive
userid: 6795
dir: disk0/00/03/18/66
datestamp: 2022-07-06 07:02:07
lastmod: 2022-07-13 06:21:47
status_changed: 2022-07-06 07:02:07
type: doctoralThesis
metadata_visibility: show
creators_name: Tanasic, Dajana
title: Intracellular membrane trafficking of 
E-cadherin in Drosophila
subjects: 570
divisions: 160100
divisions: 50000
divisions: 61002
divisions: 63600
divisions: 64900
adv_faculty: af-14
cterms_swd: Drosophila
cterms_swd: E-cadherin
cterms_swd: Trafficking
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.
date: 2022
id_scheme: DOI
id_number: 10.11588/heidok.00031866
ppn_swb: 1809417538
own_urn: urn:nbn:de:bsz:16-heidok-318665
date_accepted: 2022-07-01
advisor: HASH(0x564e1c531d08)
language: eng
bibsort: TANASICDAJINTRACELLU2022
full_text_status: public
place_of_pub: Heidelberg
citation:   Tanasic, Dajana  (2022) Intracellular membrane trafficking of E-cadherin in Drosophila.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/31866/1/Intracelluar%20membrane%20trafficking%20of%20Drosophila_Tanasic.pdf