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Multifaceted control of E-cadherin dynamics by Adaptor Protein Complex 1 during epithelial morphogenesis

Multifaceted control of E-cadherin dynamics by Adaptor Protein Complex 1 during epithelial morphogenesis
Multifaceted control of E-cadherin dynamics by Adaptor Protein Complex 1 during epithelial morphogenesis
Intracellular trafficking regulates the distribution of transmembrane proteins including the key determinants of epithelial polarity and adhesion. The Adaptor Protein 1 (AP-1) complex is the key regulator of vesicle sorting, which binds many specific cargoes. We examined roles of the AP-1 complex in epithelial morphogenesis, using the Drosophila wing as a paradigm. We found that AP-1 knockdown leads to ectopic tissue folding, which is consistent with the observed defects in integrin targeting to the basal cell-extracellular matrix adhesion sites. This occurs concurrently with an integrin-independent induction of cell death, which counteracts elevated proliferation and prevents hyperplasia. We discovered a distinct pool of AP-1 that localizes at the subapical adherens junctions. Upon AP-1 knockdown, E-cadherin is hyperinternalized from these junctions and becomes enriched at the Golgi and recycling endosomes. We then provide evidence that E-cadherin hyperinternalization acts upstream of cell death in a potential tumor-suppressive mechanism. Simultaneously, cells compensate for elevated internalization of E-cadherin by increasing its expression to maintain cell-cell adhesion.
1059-1524
ar80
Moreno, Miguel Ramirez
22b64166-df15-46e0-b5a5-2e99ea81d0da
Boswell, Katy
7496b015-dbde-4d88-afa7-d2dd71fad785
Casbolt, Helen
6606d865-8338-425e-bf46-e0732746ada9
Bulgakova, Natalia A.
f01bab85-42b3-403b-926c-3b56b17de5dd
Moreno, Miguel Ramirez
22b64166-df15-46e0-b5a5-2e99ea81d0da
Boswell, Katy
7496b015-dbde-4d88-afa7-d2dd71fad785
Casbolt, Helen
6606d865-8338-425e-bf46-e0732746ada9
Bulgakova, Natalia A.
f01bab85-42b3-403b-926c-3b56b17de5dd

Moreno, Miguel Ramirez, Boswell, Katy, Casbolt, Helen and Bulgakova, Natalia A. (2022) Multifaceted control of E-cadherin dynamics by Adaptor Protein Complex 1 during epithelial morphogenesis. Molecular Biology of the Cell, 33 (9), ar80, [ar80]. (doi:10.1091/mbc.e21-12-0598).

Record type: Article

Abstract

Intracellular trafficking regulates the distribution of transmembrane proteins including the key determinants of epithelial polarity and adhesion. The Adaptor Protein 1 (AP-1) complex is the key regulator of vesicle sorting, which binds many specific cargoes. We examined roles of the AP-1 complex in epithelial morphogenesis, using the Drosophila wing as a paradigm. We found that AP-1 knockdown leads to ectopic tissue folding, which is consistent with the observed defects in integrin targeting to the basal cell-extracellular matrix adhesion sites. This occurs concurrently with an integrin-independent induction of cell death, which counteracts elevated proliferation and prevents hyperplasia. We discovered a distinct pool of AP-1 that localizes at the subapical adherens junctions. Upon AP-1 knockdown, E-cadherin is hyperinternalized from these junctions and becomes enriched at the Golgi and recycling endosomes. We then provide evidence that E-cadherin hyperinternalization acts upstream of cell death in a potential tumor-suppressive mechanism. Simultaneously, cells compensate for elevated internalization of E-cadherin by increasing its expression to maintain cell-cell adhesion.

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Accepted/In Press date: 17 May 2022
e-pub ahead of print date: 21 July 2022
Published date: 1 August 2022
Additional Information: Funding Information: We thank Nick Brown, Iwan Evans, Roland Le Borgne, and Tsubasa Tanaka for reagents; the University of Sheffield’s Wolfson Light Microscopy and Fly Facilities for their technical support; and Kyra Campbell and David Strutt for reagents and critical feedback on the manuscript. This work was supported by a grant from the Biotechnology and Biological Sciences Research Council, UK Research and Innovation (BB/P007503/1) to N.A.B. and a summer studentship from the Genetics Society and Think Ahead SURE scheme (University of Sheffield) to M.R.M. and K.B. Publisher Copyright: © 2022 Ramírez Moreno et al.

Identifiers

Local EPrints ID: 472915
URI: http://eprints.soton.ac.uk/id/eprint/472915
ISSN: 1059-1524
PURE UUID: 2712ed1f-e779-4f00-997a-2536e6e29a13
ORCID for Miguel Ramirez Moreno: ORCID iD orcid.org/0000-0003-1559-8976

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Date deposited: 05 Jan 2023 19:17
Last modified: 06 Jun 2024 02:15

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Contributors

Author: Miguel Ramirez Moreno ORCID iD
Author: Katy Boswell
Author: Helen Casbolt
Author: Natalia A. Bulgakova

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