The major laminin receptor of mouse embryonic stem cells is a novel isoform of the α6β1 integrin

Abstract

Laminin is the first extracellular matrix protein expressed in the developing mouse embryo. It is known to influence morphogenesis and affect cell migration and polarization. Several laminin receptors are included in the integrin family of extracellular matrix receptors. Ligand binding by integrin heterodimers results in signal transduction events controlling cell motility. We report that the major laminin receptor on murine embryonic stem (ES) cells is the integrin heterodimer α6β1, an important receptor for laminin in neurons, lymphocytes, macrophages, fibroblasts, platelets and other cell types. However, the cytoplasmic domain of the ES cell α6 (α6B) differs totally from the reported cytoplasmic domain amino acid sequence of α6 (α6A). Comparisons of α6 cDNAs from ES cells and other cells suggest that the α6A and α6B cytoplasmic domains derive from alternative mRNA splicing. Anti-peptide antibodies to α6A are unreactive with ES cells, but react with mouse melanoma cells and embryonic fibroblasts. When ES cells are cultured under conditions that permit their differentiation, they become positive for α6A, concurrent with the morphologic appearance of differentiated cell types. Thus, expression of the α6Bβ1 laminin receptor may be favored in undifferentiated, totipotent cells, while the expression of α6Aβ1 receptor occurs in committed lineages. While the functions of integrin α chain cytoplasmic domains are not understood, it is possible that they contribute to transferring signals to the cell interior, e.g., by delivering cytoskeleton organizing signals in response to integrin engagement with extracellular matrix ligands. It is therefore reasonable to propose that the cellular responses to laminin may vary, according to what α subunit isoform (α6A or α6B) is expressed as part of the α6β1 laminin receptor. The switch from α6B to α6A, if confirmed in early embryos, could then be of striking potential relevance to the developmental role of laminin.