Conserved regions in the cytoplasmic domains of the leukocyte integrin αLβ2 are involved in endoplasmic reticulum retention, dimerization, and cytoskeletal association

Ruggero Pardi, Giovanna Bossi, Luca Inverardi, Ermanna Rovida, Jeffrey R. Bender

Research output: Contribution to journalArticlepeer-review

Abstract

Selected functions of integrins, including regulated cytoskeletal association and transmembrane signaling, depend on a poorly defined bidirectional communication between the extracellular and cytoplasmic domains of the a and β subunits. To investigate this problem in the leukocyte integrin α1β2 (LFA-1), we generated a series of cytoplasmic truncation or internal substitution mutants of the α1 and β2 cytoplasmic domains, and assessed their biochemical and functional properties upon ectopic expression in constitutively adherent cells. Expression of the α1β2 heterodimer in stably adherent cells is sufficient to promote its constitutive cytoskeletal association. Structural determinants for such association are located in selected regions of the β2 cytoplasmic domain, which display functional interdependence. In addition, a conserved region (Arg733-Lys742) in the β2 cytoplasmic domain seems to be critical not only for its cytoskeletal association, but also for endoplasmic reticulum retention, assembly, and transport to the plasma membrane of the mature α1β2 heterodimer. Analysis of deletion mutants of the α1 subunit demonstrates a role of the conserved, membrane-proximal GFFKR motif in conferring stability to the αβ complex, possibly because of its direct involvement in heterodimer formation. We propose that a previously uncharacterized association of defined subregions of the cytoplasmic domains of integrin a and β subunits affects the dimerization and regulated function of the adhesion receptor.

Original languageEnglish
Pages (from-to)1252-1263
Number of pages12
JournalJournal of Immunology
Volume155
Issue number3
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology

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