Role of gangliosides in the association of ErbB2 with lipid rafts in mammary epithelial HC11 cells

Elena Sottocornola, Roberta Misasi, Vincenzo Mattei, Laura Ciarlo, Roberto Gradini, Tina Garofalo, Bruno Berra, Irma Colombo, Maurizio Sorice

Research output: Contribution to journalArticle

Abstract

We analyzed the role of gangliosides in the association of the ErbB2 receptor tyrosine-kinase (RTK) with lipid rafts in mammary epithelial HC11 cells. Scanning confocal microscopy experiments revealed a strict ErbB2-GM3 colocalization in wild-type cells. In addition, analysis of membrane fractions obtained using a linear sucrose gradient showed that ErbB2, epidermal growth factor receptor (EGFR) and Shc-p66 (proteins correlated with the ErbB2 signal transduction pathway) were preferentially enriched in lipid rafts together with gangliosides. Blocking of endogenous ganglioside synthesis by (+/-)-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol hydrochloride ([D]-PDMP) induced a drastic cell-surface redistribution of ErbB2, EGFR and Shc-p66, within the Triton-soluble fractions, as revealed by linear sucrose-gradient analysis. This redistribution was partially reverted when exogenous GM3 was added to ganglioside-depleted HC11 cells. The results point out the key role of ganglioside GM3 in retaining ErbB2 and signal-transduction- correlated proteins in lipid rafts.

Original languageEnglish
Pages (from-to)1821-1830
Number of pages10
JournalFEBS Journal
Volume273
Issue number8
DOIs
Publication statusPublished - Apr 2006

Keywords

  • Epidermal growth factor receptor
  • ErbB2
  • GM3
  • HC11 cells
  • Lipid rafts

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Sottocornola, E., Misasi, R., Mattei, V., Ciarlo, L., Gradini, R., Garofalo, T., Berra, B., Colombo, I., & Sorice, M. (2006). Role of gangliosides in the association of ErbB2 with lipid rafts in mammary epithelial HC11 cells. FEBS Journal, 273(8), 1821-1830. https://doi.org/10.1111/j.1742-4658.2006.05203.x