EphA2 Transmembrane Domain Is Uniquely Required for Keratinocyte Migration by Regulating Ephrin-A1 Levels

Rosa Ventrella, Nihal Kaplan, Paul Hoover, Bethany Elena Perez-White, Robert M Lavker, Spiro Getsios*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


EphA2 receptor tyrosine kinase is activated by ephrin-A1 ligand, which harbors a glycosylphosphatidylinositol anchor that enhances lipid raft localization. Although EphA2 and ephrin-A1 modulate keratinocyte migration and differentiation, the ability of this cell-cell communication complex to localize to different membrane regions in keratinocytes remains unknown. Using a combination of biochemical and imaging approaches, we provide evidence that ephrin-A1 and a ligand-activated form of EphA2 partition outside of lipid raft domains in response to calcium-mediated cell-cell contact stabilization in normal human epidermal keratinocytes. EphA2 transmembrane domain swapping with a shorter and molecularly distinct transmembrane domain of EphA1 resulted in decreased localization of this receptor tyrosine kinase at cell-cell junctions and increased expression of ephrin-A1, which is a negative regulator of keratinocyte migration. Accordingly, altered EphA2 membrane distribution at cell-cell contacts limited the ability of keratinocytes to seal linear scratch wounds in vitro in an ephrin-A1–dependent manner. Collectively, these studies highlight a key role for the EphA2 transmembrane domain in receptor-ligand membrane distribution at cell-cell contacts that modulates ephrin-A1 levels to allow for efficient keratinocyte migration with relevance for cutaneous wound healing.

Original languageEnglish (US)
Pages (from-to)2133-2143
Number of pages11
JournalJournal of Investigative Dermatology
Issue number10
StatePublished - Oct 2018

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry
  • Cell Biology


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