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Endosome-Localized Clathrin Adaptors AP-1 and GGA2 Support Cell Surface Expression of a Subset of RTKs for Cell Growth

69 Pages Posted: 3 Jun 2020 Sneak Peek Status: Under Review

See all articles by Takefumi Uemura

Takefumi Uemura

Fukushima Medical University - Department of Anatomy and Histology

Takehiro Suzuki

RIKEN Center for Sustainable Resource Science - Biomolecular Characterization

Naoshi Dohmae

RIKEN Center for Sustainable Resource Science - Biomolecular Characterization

Satoshi Waguri

Fukushima Medical University - Department of Anatomy and Histology

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Abstract

The role of Golgi/endosome-localized clathrin adaptors in the maintenance of steady-state cell surface receptor tyrosine kinases (RTKs) is not well known. Here, we show that the epidermal growth factor receptor (EGFR), an RTK, associates preferentially with both AP-1 and GGA2 in vitro. AP-1 depletion reduces the expression of EGFR protein by promoting its lysosomal degradation. Proximity ligation assays demonstrated that the interaction of EGFR with AP-1 or GGA2 occurs in Rab11-positive recycling endosomes. Western blot analysis revealed that the depletion of AP-1 or GGA2 decreased surface expression of additional RTKs, such as Erb-B4 and MET. AP-1 depletion suppressed the growth of H1975 cancer cells and normal ARPE-19 cells. AP-1 was expressed in endosomes at high levels in several cancer tissues. Collectively, these results indicate that AP-1 and GGA2 function to retrieve a subset of RTKs in recycling endosomes, thereby sustaining their cell surface expression and, consequently, cancer cell growth.

Keywords: receptor tyrosine kinase, EGFR, AP-1 complex, GGA2, Recycling endosome, cancer

Suggested Citation

Uemura, Takefumi and Suzuki, Takehiro and Dohmae, Naoshi and Waguri, Satoshi, Endosome-Localized Clathrin Adaptors AP-1 and GGA2 Support Cell Surface Expression of a Subset of RTKs for Cell Growth. Available at SSRN: https://ssrn.com/abstract=3600559 or http://dx.doi.org/10.2139/ssrn.3600559
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Takefumi Uemura

Fukushima Medical University - Department of Anatomy and Histology

Japan

Takehiro Suzuki

RIKEN Center for Sustainable Resource Science - Biomolecular Characterization

2-1 Hirosawa
Bioscience Building
Wako, Saitama, 351-0198
Japan

Naoshi Dohmae

RIKEN Center for Sustainable Resource Science - Biomolecular Characterization

2-1 Hirosawa
Bioscience Building
Wako, Saitama, 351-0198
Japan

Satoshi Waguri (Contact Author)

Fukushima Medical University - Department of Anatomy and Histology ( email )

Japan

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