Laminins of the neuromuscular system.

Abstract

The mammalian neuromuscular system expresses seven laminin genes (alpha 1, alpha 2, alpha 4, alpha 5, beta 1, beta 2, and gamma 1), produces seven isoforms of the laminin trimer (laminins 1, 2, 4, 8, 9, 10, and 11), and distributes these trimers to at least seven distinct basal laminae (perineurial, endoneurial, terminal Schwann cell, myotendinous junction, synaptic cleft, synaptic fold, and extrajunctional muscle). The patterns of expression, assembly, and distribution are regulated during development, and primary and secondary changes in laminin expression occur in several neuromuscular genetic disorders. Functional studies using knockout and transgenic mice, and purified laminins and cell types, demonstrate that laminins are required components of basal laminae in the neuromuscular system. Collectively, laminins have both structural and signaling functions; individually, laminin isoforms have unique roles in regulating the behavior of nerve, muscle, and Schwann cell. Among them, laminin-2 (alpha 2 beta 1 gamma 1) plays an important structural role in supporting the muscle plasma membrane, laminin-4 regulates adhesion and differentiation of the myotendinous junction, and laminin-11 regulates nerve terminal differentiation and Schwann cell motility. Together, these observations reveal remarkable diversity in the formation and function of laminins and basal laminae, and suggest avenues for addressing some neuromuscular diseases.