TY - JOUR
T1 - EHD1 and RUSC2 control basal epidermal growth factor receptor cell surface expression and recycling
AU - Tom, Eric C.
AU - Mushtaq, Insha
AU - Mohapatra, Bhopal C.
AU - Luan, Haitao
AU - Bhat, Aaqib M.
AU - Zutshi, Neha
AU - Chakraborty, Sukanya
AU - Islam, Namista
AU - Arya, Priyanka
AU - Bielecki, Timothy A.
AU - Iseka, Fany M.
AU - Bhattacharyya, Sohinee
AU - Cypher, Luke R.
AU - Goetz, Benjamin T.
AU - Negi, Simarjeet K.
AU - Storck, Matthew D.
AU - Rana, Sandeep
AU - Barnekow, Angelika
AU - Singh, Pankaj K.
AU - Ying, Guoguang
AU - Guda, Chittibabu
AU - Natarajan, Amarnath
AU - Band, Vimla
AU - Banda, Hamid
N1 - Publisher Copyright:
Copyright © 2020 American Society for Microbiology. All Rights Reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - Cell proliferation
KW - EGFR
KW - EHD1
KW - Endocytic trafficking
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U2 - 10.1128/MCB.00434-19
DO - 10.1128/MCB.00434-19
M3 - Article
C2 - 31932478
AN - SCOPUS:85082147786
SN - 0270-7306
VL - 40
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 7
M1 - e00434
ER -