Abstract
The ECM glycoprotein laminin has profound and varied actions on neurons in vitro. Little is known about how laminin's multiple domains and receptor-binding sites interact in determining its overall effects. Here, it is shown that laminin's ability to promote migration of olfactory epithelium neuronal cells maps to distal long arm domain E8 and is mediated by α 6 β 1 integrin. Surprisingly, treatment of laminin with antibodies against its short arms (domains E1′ or P1′ uncovered a new neuronal migration-promoting activity, mediated by a β 1 integrin other than α 6 β 1 Laminin treated with anti-short arm antibodies also promoted β 1 integrin-dependent neurite outgrowth from late embryonic retinal neurons, which are normally unresponsive to laminin. These “antibody-induced” migration and neurite outgrowth activities mapped to laminin's distal long arm, far from the site(s) of antibody binding. Evidence is presented that the induced activities are not actually cryptic in laminin, but are suppressed by an activity that is located in laminin's P1′ domain and that may be lacking in the laminin homolog merosin.
Highlights
The extracellular matrix (ECM) has profound effects on cells: it can influence cell shape, proliferation, motility, differentiation, growth factor responsiveness, and gene expression.The ECM glycoproteins that elicit these responses, including laminin, fibronectin, thrombospondin, tenascin, and collagens, are large, multidomain molecules, the individual domains of which appear to have distinct biological activities
In a recent study of the migration of neuronal cells derived from cultured embryonic mouse olfactory epithelium (OE), it was found that laminin stimulated and guided neuronal cell migration, but was an extremely poor substratum for cell adhesion
In contrast to E8, substrata treated with El’, E3, E4, or G supported minimal cell migration and neurite outgrowth, equivalent to that on coverslips treated with bovine serum albumin (KS/a) or with fibronectin (see Calof and OE explants were cultured on laminin-treated glass coverslips in the presence of monoclonal rat anti-a6 (GoH3), or nonimmune IgG (IO pgiml)
Summary
The extracellular matrix (ECM) has profound effects on cells: it can influence cell shape, proliferation, motility, differentiation, growth factor responsiveness, and gene expression.The ECM glycoproteins that elicit these responses, including laminin, fibronectin, thrombospondin, tenascin, and collagens, are large, multidomain molecules, the individual domains of which appear to have distinct biological activities (see reviews by Martin and Timpl, 1987; Erickson and Bourdon, 1989; Beck et al, 1990; Hynes, 1990; Lander andCalof, 1993). The ECM glycoproteins that elicit these responses, including laminin, fibronectin, thrombospondin, tenascin, and collagens, are large, multidomain molecules, the individual domains of which appear to have distinct biological activities Some of laminin’s activities have already been mapped to distinct molecular domains (reviewed by Sephel et al, 1989; Beck et al, 1990; Mecham, 1991; Reichardt and Tomaselli, 1991; Lander and Calof, 1993). The results raised the possibility that the effects of laminin on certain neurons might be mediated through some form of signaling, rather than through promotion of cell-substratum adhesion
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