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 - Funding Information:
Support was provide by the following: NIH grants CA87986 and CA105489 to H.B. and CA96844 and CA144027 to V.B.; Department of Defense grants W81XWH-17-1-0616 (H.B.) and W81XWH-07-1-0351 and W81XWH-11-1-0171 (V.B.); an NE DHHS LB506 (2018-03) grant; University of Nebraska Collaboration Initiative seed grants; pilot grants from the Fred & Pamela Buffett Cancer Center and the Pediatric Cancer Research Program at UNMC (H.B.); Institutional Development Award (IDeA) from the NIGMS of the NIH under grant number P30 GM106397; Nebraska Research Initiative Food for Health seed grant; support to UNMC core facilities from the NCI Cancer Center Support Grant (P30CA036727) to Fred & Pamela Buffett Cancer Center and the Nebraska Research Initiative; and the Raphael Bonita Memorial Fund. T.A.B., B.T.G., and L.R.C. were trainees under an NCI Cancer Biology Training Grant. I.M., N.Z., B.C.M., S.B., and P.A. received UNMC graduate assistantships. H.L. was the recipient of a China Scholarship Council graduate fellowship.
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
UR - http://www.scopus.com/inward/record.url?scp=85082147786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082147786&partnerID=8YFLogxK
U2 - 10.1128/MCB.00434-19
DO - 10.1128/MCB.00434-19
M3 - Article
C2 - 31932478
AN - SCOPUS:85082147786
VL - 40
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 7
M1 - e00434
ER -