Synaptic integrins in developing, adult, and mutant muscle: Selective association of alpha 1, alpha 7A, and alpha 7B integrins with the neuromuscular junction

Differentiation of both pre- and postsynaptic structures at the skeletal neuromuscular junction is organized by the basal lamina that occupies the synaptic cleft. As beta 1 integrins are a major class of receptors for basal lamina components, we stained muscles with antibodies to the 10 integrin alpha subunits known to form dimers with beta 1, to determine if any of these molecules were concentrated at synaptic sites on muscle fibers. In both developing and adult muscle, the integrin alpha 1 chain was selectively associated with presynaptic cells (Schwann cells and/or nerve terminals), while alpha 7 was present on both synaptic and extrasynaptic portions of the muscle fiber surface. Thus alpha 1 and alpha 7 integrins are present in synaptic membranes. Expression of the alpha 7 chain was analyzed further by staining with antibodies specific for three alternatively spliced products of the alpha 7 gene (A, B, and C), all of which were expressed in muscle. The alpha 7A and alpha 7B isoforms were confined to synaptic sites in adult muscle, while alpha 7C was present both synaptically and extrasynaptically. In developing muscle, alpha 7A appeared postnatally and specifically at the synapse; alpha 7B was present throughout the muscle fiber perinatally, becoming confined to the synapse in the second postnatal week; and alpha 7C was present extrasynaptically both perinatally and in adulthood. Thus, two of the alpha 7 integrins are synapse-specific, and all three show distinct spatiotemporal patterns of expression within a single cell type. Finally, we asked whether perturbation of laminin expression affected the distribution of the alpha 7 integrins. In normal mice, laminin beta 2 is concentrated in synaptic basal lamina. In beta 2-null mutant mice, alpha 7A was still present at synaptic sites, but alpha 7B was absent. This result provides genetic evidence that basal lamina composition is a determinant of integrin distribution. (C) 1996 Academic Press, Inc.