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 skelet al neuromuscular junction is organized by the basal lamina that occupi es the synaptic cleft. As beta 1 integrins are a major class of recept ors for basal lamina components, we stained muscles with antibodies to the 10 integrin alpha subunits known to form dimers with beta 1, to d etermine if any of these molecules were concentrated at synaptic sites on muscle fibers. In both developing and adult muscle, the integrin a lpha 1 chain was selectively associated with presynaptic cells (Schwan n cells and/or nerve terminals), while alpha 7 was present on both syn aptic and extrasynaptic portions of the muscle fiber surface. Thus alp ha 1 and alpha 7 integrins are present in synaptic membranes. Expressi on of the alpha 7 chain was analyzed further by staining with antibodi es specific for three alternatively spliced products of the alpha 7 ge ne (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. I n developing muscle, alpha 7A appeared postnatally and specifically at the synapse; alpha 7B was present throughout the muscle fiber perinat ally, becoming confined to the synapse in the second postnatal week; a nd alpha 7C was present extrasynaptically both perinatally and in adul thood. Thus, two of the alpha 7 integrins are synapse-specific, and al l three show distinct spatiotemporal patterns of expression within a s ingle cell type. Finally, we asked whether perturbation of laminin exp ression 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) 199 6 Academic Press, Inc.