EHD1 and RUSC2 Control Basal Epidermal Growth Factor Receptor Cell Surface Expression and Recycling.

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.

• Authors: 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 Ying, Chittibabu Guda, Amarnath Natarajan, Vimla Band, Hamid Band
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 40 Issue 7 (03 16 2020) ISSN: 1098-5549 [Electronic] United States
• PMID: 31932478 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2020 American Society for Microbiology.

Chemical References

• Carrier Proteins
• EHD1 protein, human
• RNA, Small Interfering
• RUSC2 protein, human
• Vesicular Transport Proteins
• EGFR protein, human
• ErbB Receptors

Topics

• Animals
• Carrier Proteins (metabolism)
• Cell Communication (physiology)
• Cell Line
• Cell Membrane (metabolism)
• Cell Proliferation (physiology)
• ErbB Receptors (metabolism)
• Golgi Apparatus (metabolism)
• Humans
• Mice
• Protein Transport (physiology)
• RNA Interference
• RNA, Small Interfering (genetics)
• Vesicular Transport Proteins (genetics, metabolism)