SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis

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SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis

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dc.contributor.author Oh, Hyejin en_US
dc.contributor.author Kim, Hwan en_US
dc.contributor.author Chung, Kyung-Hwun en_US
dc.contributor.author Hong, Nan Hyung en_US
dc.contributor.author Shin, Baehyun en_US
dc.contributor.author Park, Woo Jin en_US
dc.contributor.author Jun, Youngsoo en_US
dc.contributor.author Rhee, Sangmyung en_US
dc.contributor.author Song, Woo Keun en_US
dc.date.accessioned 2014-03-11T10:17:08Z
dc.date.issued 2013 en_US
dc.identifier.citation Oh, 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.issn 1932-6203 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879345
dc.description.abstract The 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.iso en_US en
dc.publisher Public Library of Science en
dc.relation.isversionof doi:10.1371/journal.pone.0082610 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858329/pdf/ en
dash.license LAA en_US
dc.title SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal PLoS ONE en
dc.date.available 2014-03-11T10:17:08Z

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