Cell surface expression of integrin β4-subunit in the absence of α6-subunit

Abstract

<div lang="en" class="abs"><p class="abs_header">Abstract</p><p>Laminin-rich basement membrane (BM) guides epithelial cell polarity, regulates epithelial cell behavior and maintains the integrity of epithelial tissues. αβ1- and α6β4-integrins both contribute to laminin adhesion and signaling via the assembly of integrin adhesion complexes that help to orient the apico-basal polarity axis. β4-integrin differs from other integrin subunits due to its large cytoplasmic domain that connects to cellular intermediate filament (IF) networks in specialized adhesions called hemidesmosomes (HD). β4-integrin is only known to form a heterodimer with the α6-subunit. In normal tissues, β4-integrin is expressed in cells that also express the α6-subunit. However, in most cells analyzed, β4-integrin is expressed in large excess over α6-integrin and in some tumor cells, β4-integrin appears to promote tumorigenic signaling despite loss of HDs formation. The fate of free β4-subunit and its potential functions in cells have not been extensively studied. Here, we have studied subcellular localization and potential surface delivery of β4-integrin in the absence of its heterodimer partner α6. We provide evidence that a significant fraction of β4-subunit can reach the cell surface without α6-subunit. We also report that β4 is cleaved at its extracellular domain to produce a membrane-bound proteolytic product with an intact cytoplasmic domain. The processed β4-integrin did not co-precipitate with α6-subunit. Taken together, our data suggest that β4-integrin might have functions that are independent of heterodimer formation.</p></div>