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

Sottocornola, E.; Misasi, R.; Mattei, V.; Ciarlo, L.; Gradini, R.; Garofalo, T.; Berra, B.; Colombo, I.; Sorice, M.

Febs Journal 273(8): 1821-1830

2006


ISSN/ISBN: 1742-464X
PMID: 16623716
DOI: 10.1111/j.1742-4658.2006.05203.x
Accession: 004470228

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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.

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