Spatial organization of epha2 at the cell-cell interface modulates trans-endocytosis of ephrina1

Adrienne C. Greene, Samuel J. Lord, Aiwei Tian, Christopher Rhodes, Hiroyuki Kai, Jay T. Groves

研究成果: Article査読

30 被引用数 (Scopus)

抄録

EphA2 is a receptor tyrosine kinase (RTK) that is sensitive to spatial and mechanical aspects of the cell's microenvironment. Misregulation of EphA2 occurs in many aggressive cancers. Although its juxtacrine signaling geometry (EphA2's cognate ligand ephrinA1 is expressed on the surface of an apposing cell) provides a mechanism by which the receptor may experience extracellular forces, this also renders the system challenging to decode. By depositing living cells on synthetic supported lipid membranes displaying ephrinA1, we have reconstituted key features of the juxtacrine EphA2-ephrinA1 signaling system while maintaining the ability to perturb the spatial and mechanical properties of the membrane-cell interface with precision. In addition, we developed a trans-endocytosis assay to monitor internalization of ephrinA1 from a supported membrane into the apposing cell using a quantitative three-dimensional fluorescence microscopy assay. Using this experimental platform to mimic a cell-cell junction, we found that the signaling complex is not efficiently internalized when lateral reorganization at the membrane-cell contact sites is physically hindered. This suggests that EphA2-ephrinA1 trans-endocytosis is sensitive to the mechanical properties of a cell's microenvironment and may have implications in physical aspects of tumor biology.

本文言語English
ページ(範囲)2196-2205
ページ数10
ジャーナルBiophysical Journal
106
10
DOI
出版ステータスPublished - 2014 5 20
外部発表はい

ASJC Scopus subject areas

  • 生物理学

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