Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth

Abstract The role of Golgi/endosome-localized clathrin adapters in the maintenance of steady-state cell surface epidermal growth factor receptor (EGFR) is not well known. Here, we show that EGFR associates preferentially with both AP-1 and GGA2 in vitro. AP-1 depletion caused a reduction in the EGFR...

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Autores principales:	Takefumi Uemura, Takehiro Suzuki, Naoshi Dohmae, Satoshi Waguri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/141cef8827ce44c189674d485234760b
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spelling	oai:doaj.org-article:141cef8827ce44c189674d485234760b2021-11-21T12:15:22ZClathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth10.1038/s41389-021-00367-22157-9024https://doaj.org/article/141cef8827ce44c189674d485234760b2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41389-021-00367-2https://doaj.org/toc/2157-9024Abstract The role of Golgi/endosome-localized clathrin adapters in the maintenance of steady-state cell surface epidermal growth factor receptor (EGFR) is not well known. Here, we show that EGFR associates preferentially with both AP-1 and GGA2 in vitro. AP-1 depletion caused a reduction in the EGFR protein by promoting its lysosomal degradation. Triple immunofluorescence microscopy and proximity ligation assays demonstrated that the interaction of EGFR with AP-1 or GGA2 occurred more frequently in Rab11-positive recycling endosomes than in Rab5-positive early endosomes. Biochemical recycling assay revealed that the depletion of AP-1 or GGA2 significantly suppressed EGFR recycling to the plasma membrane regardless of the EGF stimulation. Depletion of AP-1 or GGA2 also reduced cell contents of other tyrosine kinases, MET and ErbB4, and therefore, suppressed the growth of H1975 cancer cells in culture and xenograft model. Moreover, AP-1 was expressed in endosomes at higher levels in some cancer tissues. Collectively, these results suggest that AP-1 and GGA2 function in recycling endosomes to retrieve endocytosed EGFR, thereby sustaining its cell surface expression and, consequently, cancer cell growth.Takefumi UemuraTakehiro SuzukiNaoshi DohmaeSatoshi WaguriNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncogenesis, Vol 10, Iss 11, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Takefumi Uemura Takehiro Suzuki Naoshi Dohmae Satoshi Waguri Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth
description	Abstract The role of Golgi/endosome-localized clathrin adapters in the maintenance of steady-state cell surface epidermal growth factor receptor (EGFR) is not well known. Here, we show that EGFR associates preferentially with both AP-1 and GGA2 in vitro. AP-1 depletion caused a reduction in the EGFR protein by promoting its lysosomal degradation. Triple immunofluorescence microscopy and proximity ligation assays demonstrated that the interaction of EGFR with AP-1 or GGA2 occurred more frequently in Rab11-positive recycling endosomes than in Rab5-positive early endosomes. Biochemical recycling assay revealed that the depletion of AP-1 or GGA2 significantly suppressed EGFR recycling to the plasma membrane regardless of the EGF stimulation. Depletion of AP-1 or GGA2 also reduced cell contents of other tyrosine kinases, MET and ErbB4, and therefore, suppressed the growth of H1975 cancer cells in culture and xenograft model. Moreover, AP-1 was expressed in endosomes at higher levels in some cancer tissues. Collectively, these results suggest that AP-1 and GGA2 function in recycling endosomes to retrieve endocytosed EGFR, thereby sustaining its cell surface expression and, consequently, cancer cell growth.
format	article
author	Takefumi Uemura Takehiro Suzuki Naoshi Dohmae Satoshi Waguri
author_facet	Takefumi Uemura Takehiro Suzuki Naoshi Dohmae Satoshi Waguri
author_sort	Takefumi Uemura
title	Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth
title_short	Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth
title_full	Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth
title_fullStr	Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth
title_full_unstemmed	Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth
title_sort	clathrin adapters ap-1 and gga2 support expression of epidermal growth factor receptor for cell growth
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/141cef8827ce44c189674d485234760b
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Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth

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