Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand.
Bottom Line: In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2.This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway.Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line.
Affiliation: Laboratory of Nano-Biotechnology, Department of Medical Bioengineering Science, Graduate School of Natural Science and Biotechnology, Okayama University, Kita-ku, Okayama, Japan.Show MeSH
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Mentions: Cells adopt divergent pathways for the endocytosis of the cargos and receptors. The key pathways were categorized into clathrin-dependent and clathrin-independent mechanisms . The clathrin-independent pathway is further classified into caveolar and GPI-anchored early endocytic compartments (GEEC) pathways [33, 34]. ErbB2 is thought to be internalizing in SK-OV-3 through clathrin-mediated internalization . In this study we found that the mechanism of internalization of ErbB2 present in SK-OV-3 cells is deficient in SK-BR-3 cells. We tried to identify the difference between the two cell lines using DNA microarray (Fig. S2). As a result the expression of claudin 16, caveolin-1 and caveolin-2 were found to be extensively down-regulated in SK-BR-3 cells when compared to SK-OV-3 cells. This absence of caveolin-1 in SK-BR-3 cells was further confirmed by immunostaining using anti-Cav1 antibody (Fig. 5A). SK-BR-3 did not show the presence of caveolin-1 suggesting that the impaired caveolar mechanism prevailing in the cell, which was consistent with the finding by the previous reports [13, 35]. Because caveolin-1 was detected in SK-OV-3 cells the internalization pathway deficient in SK-BR-3 cells might be attributed to caveolae.
Affiliation: Laboratory of Nano-Biotechnology, Department of Medical Bioengineering Science, Graduate School of Natural Science and Biotechnology, Okayama University, Kita-ku, Okayama, Japan.