EHD1 and RUSC2 control basal epidermal growth factor receptor cell surface expression and recycling

Eric C. Tom, Insha Mushtaq, Bhopal C. Mohapatra, Haitao Luan, Aaqib M. Bhat, Neha Zutshi, Sukanya Chakraborty, Namista Islam, Priyanka Arya, Timothy A. Bielecki, Fany M. Iseka, Sohinee Bhattacharyya, Luke R. Cypher, Benjamin T. Goetz, Simarjeet K. Negi, Matthew D. Storck, Sandeep Rana, Angelika Barnekow, Pankaj K. Singh, Guoguang YingChittibabu Guda, Amarnath Natarajan, Vimla Band, Hamid Banda

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere00434
JournalMolecular and cellular biology
Volume40
Issue number7
DOIs
StatePublished - Apr 1 2020

Keywords

  • Cell proliferation
  • EGFR
  • EHD1
  • Endocytic trafficking

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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