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dc.contributor.authorOh, Hyejinen_US
dc.contributor.authorKim, Hwanen_US
dc.contributor.authorChung, Kyung-Hwunen_US
dc.contributor.authorHong, Nan Hyungen_US
dc.contributor.authorShin, Baehyunen_US
dc.contributor.authorPark, Woo Jinen_US
dc.contributor.authorJun, Youngsooen_US
dc.contributor.authorRhee, Sangmyungen_US
dc.contributor.authorSong, Woo Keunen_US
dc.date.accessioned2014-03-11T10:17:08Z
dc.date.issued2013en_US
dc.identifier.citationOh, Hyejin, Hwan Kim, Kyung-Hwun Chung, Nan Hyung Hong, Baehyun Shin, Woo Jin Park, Youngsoo Jun, Sangmyung Rhee, and Woo Keun Song. 2013. “SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis.” PLoS ONE 8 (12): e82610. doi:10.1371/journal.pone.0082610. http://dx.doi.org/10.1371/journal.pone.0082610.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879345
dc.description.abstractThe finding that SPIN90 colocalizes with epidermal growth factor (EGF) in EEA1-positive endosomes prompted us to investigate the role of SPIN90 in endocytosis of the EGF receptor (EGFR). In the present study, we demonstrated that SPIN90 participates in the early stages of endocytosis, including vesicle formation and trafficking. Stable HeLa cells with knockdown of SPIN90 displayed significantly higher levels of surface EGFR than control cells. Analysis of the abundance and cellular distribution of EGFR via electron microscopy revealed that SPIN90 knockdown cells contain residual EGFR at cell membranes and fewer EGFR-containing endosomes, both features that reflect reduced endosome formation. The delayed early endosomal targeting capacity of SPIN90 knockdown cells led to increased EGFR stability, consistent with the observed accumulation of EGFR at the membrane. Small endosome sizes and reduced endosome formation in SPIN90 knockdown cells, observed using fluorescent confocal microscopy, strongly supported the involvement of SPIN90 in endocytosis of EGFR. Overexpression of SPIN90 variants, particularly the SH3, PRD, and CC (positions 643 - 722) domains, resulted in aberrant morphology of Rab5-positive endosomes (detected as small spots located near the cell membrane) and defects in endosomal movement. These findings clearly suggest that SPIN90 participates in the formation and movement of endosomes. Consistent with this, SPIN90 knockdown enhanced cell proliferation. The delay in EGFR endocytosis effectively increased the levels of endosomal EGFR, which triggered activation of ERK1/2 and cell proliferation via upregulation of cyclin D1. Collectively, our findings suggest that SPIN90 contributes to the formation and movement of endosomal vesicles, and modulates the stability of EGFR protein, which affects cell cycle progression via regulation of the activities of downstream proteins, such as ERK1/2, after EGF stimulation.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0082610en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858329/pdf/en
dash.licenseLAAen_US
dc.titleSPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosisen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dc.date.available2014-03-11T10:17:08Z
dc.identifier.doi10.1371/journal.pone.0082610*


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