Connecting to the laminin network

Abstract

The laminins are a growing family of proteins that fulfil a structural role in basement membranes. This role is manifested in genetic diseases such as epidermolysis bullosa and congenital muscular dystrophies caused by mutations in genes encoding laminins. In addition to their role as mechanical links, laminins in vitro have a number of biological effects, such as promoting cell adhesion, cell polarization, differentiation, neurite extension and preventing apoptosis. These latter effects involve cell-surface receptors and intracellular signalling. In furthering the understanding of the biological role of different domains in laminin, the elegant paper by Colognato et al. investigates the effects of polymerizing and nonpolymerizing laminin on muscle cell responses1. The data show that, in a muscle cell line, α7β1 integrin and dystroglycan act as nucleation points for laminin assembly by binding to the C-terminal part of laminin-1. The subsequent formation of a laminin network, which in turn leads to receptor reorganization, was found to require actin reorganization and tyrosine phosphorylation. However, when nonpolymerizing laminin was used, the reorganization of laminin receptors and cytoskeleton did not occur. These data are especially interesting with respect to congenital muscular dystrophies. Some of the characterized laminin α2 chain mutations create laminins that are predicted to be nonpolymerizing forms. Thus, although these mutated laminins are capable of binding to cell-surface receptors, they are not predicted to assemble into laminin networks. This might explain how mutations in a region not involved in cell binding, by affecting the laminin polymerization status, still can affect cell signalling. Further in vitro analysis of polymerized/nonpolymerized laminins are likely to prove fruitful in the understanding of the biological role of laminins in vivo.