LAMININ VARIANTS - WHY, WHERE AND WHEN

Laminin is a member of a family of proteins that are composed of three subunits, one heavy chain and two light chains. Five subunits in the laminin family have been cloned and sequenced so far. These include two heavy chains, the laminin A chain and the merosin M chain, and three light chains, B1, B2, and S. These five subunits can form four different laminin variants: A-B1-B2, A-S-B2, M-B1-B2, and M-S-B2, all having the B2 chain in common. Major basement membranes in tissues contain at least one of the four laminin variants. For example, the adult muscle and nerve basement membranes contain M-B1-B2, smooth muscle contains A-B1-B2, the myotendinous junction and the trophoblast basement membrane in the placenta contain M-S-B2, and blood vessels contain A-B1-B2 and/or A-S-B2. In the brain, the merosin M chain is present in association with neuronal fibers. The four members of the laminin family interact with cells in a similar manner. Thus, they promote outgrowth of neurites from neuronal cells and promote attachment and spreading of non-neuronal cells. The interaction of cells with laminins is mediated largely by integrin type receptors, including integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta1. The expression of the different laminin-like proteins is developmentally regulated. The laminin A chain is the first heavy chain expressed. It is present in the striated muscle basement membrane in the fetus, but its expression is gradually decreased during development and it is restricted to the synaptic basement membrane in the adult. In contrast, the expression of the M chain in muscle is induced around birth and increases until it is the predominant heavy chain made in the mature muscle. The differential expression of laminin variants in tissues during different times of development suggest that the laminin variants have specialized functions. The structural and functional comparisons of existing variants as well as of variants yet to be discovered should further our understanding of the effects of basement membranes on cell behavior.