Contrasting roles for integrin β1 and β5 cytoplasmic domains in subcellular localization, cell proliferation, and cell migration

Renata Pasqualini, Martin E. Hemler

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

To carry out a detailed comparison of the roles of integrin β1 and β5 cytoplasmic domains, we expressed both wild type β1 and chimeric β(1/5) constructs in CHO cells. In the latter, the cytoplasmic domain of β1 was replaced with that of β5. The human β1 and β(1/5) constructs appeared at similar levels at the cell surface (mostly as α5β1 heterodimers) and contributed equally to CHO cell adhesion to fibronectin. However, β1 but not β(1/5) localized to focal adhesion-like structures when CHO cells were spread on fibronectin. Furthermore, only the β1-CHO cells showed increased proliferation in response to fibronectin plus an integrin-activating anti- β1 antibody, and showed increased appearance of 32P-labeled protein (p90) that correlated with proliferation. In sharp contrast, the β(1/5)-CHO cells were notably more migratory than β1-CHO cells in a transwell haptotactic migration assay. These results indicate that the β1 and β5 integrin subunit cytoplasmic domains can translate similar adhesive information into highly contrasting subsequent events. Thus, we have established that 'inside- out' and 'outside-in' integrin signaling pathways are regulated by fundamentally distinct mechanisms. In addition, we suggest that the same properties of the β1 cytoplasmic domain that promote recruitment to visible focal adhesion-like structures may also be conducive to cell proliferation. Conversely, the properties of the β5 tail that make it less likely to localize into focal adhesion-like structures may contribute to enhanced cell migration.

Original languageEnglish (US)
Pages (from-to)447-460
Number of pages14
JournalJournal of Cell Biology
Volume125
Issue number2
DOIs
StatePublished - Apr 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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