EHD1 and RUSC2 Control Basal Epidermal Growth Factor Receptor Cell Surface Expression and Recycling
| Autor: | Namista Islam, Sohinee Bhattacharyya, Bhopal Mohapatra, Matthew D. Storck, Hamid Band, Simarjeet K. Negi, Guoguang Ying, Amarnath Natarajan, Priyanka Arya, Aaqib M. Bhat, Neha Zutshi, Fany Iseka, Sukanya Chakraborty, Timothy A. Bielecki, Pankaj K. Singh, Insha Mushtaq, Eric Tom, Vimla Band, Luke R. Cypher, Haitao Luan, Benjamin T. Goetz, Chittibabu Guda, Angelika Barnekow, Sandeep Rana |
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| Rok vydání: | 2019 |
| Předmět: |
Endocytic cycle
Cell Vesicular Transport Proteins Golgi Apparatus Cell Communication Receptor tyrosine kinase Cell Line 03 medical and health sciences symbols.namesake Mice 0302 clinical medicine medicine Animals Humans Epidermal growth factor receptor RNA Small Interfering Molecular Biology 030304 developmental biology Cell Proliferation 0303 health sciences Gene knockdown biology Cell growth Cell Membrane Cell Biology Golgi apparatus Phenotype Cell biology ErbB Receptors Protein Transport medicine.anatomical_structure 030220 oncology & carcinogenesis symbols biology.protein RNA Interference Carrier Proteins Research Article |
| Zdroj: | Mol Cell Biol |
| ISSN: | 1098-5549 |
| Popis: | Epidermal growth factor receptor (EGFR) is a prototype receptor tyrosine kinase and an oncoprotein in many solid tumors. Cell surface display of EGFR is essential for cellular responses to its ligands. While postactivation endocytic trafficking of EGFR has been well elucidated, little is known about mechanisms of basal/preactivation surface display of EGFR. Here, we identify a novel role of the endocytic regulator EHD1 and a potential EHD1 partner, RUSC2, in cell surface display of EGFR. EHD1 and RUSC2 colocalize with EGFR in vesicular/tubular structures and at the Golgi compartment. Inducible EHD1 knockdown reduced the cell surface EGFR expression with accumulation at the Golgi compartment, a phenotype rescued by exogenous EHD1. RUSC2 knockdown phenocopied the EHD1 depletion effects. EHD1 or RUSC2 depletion impaired the EGF-induced cell proliferation, demonstrating that the novel, EHD1- and RUSC2-dependent transport of unstimulated EGFR from the Golgi compartment to the cell surface that we describe is functionally important, with implications for physiologic and oncogenic roles of EGFR and targeted cancer therapies. |
| Databáze: | OpenAIRE |
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