Molecular heterogeneity of basal laminae: isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere.
Laminin and collagen IV are components of most basal laminae (BLs). Recently, both have been shown to be products of multigene families. The A, B1, and B2 subunits of the laminin trimer are products of related genes, and the BL components merosin M and s-laminin are homologues of the A and B1 subunits, respectively. Similarly, five related collagen IV chains, alpha 1(IV)-alpha 5(IV), have been described. Here, we used a panel of subunit-specific antibodies to determine the distribution of the laminin and collagen IV isoforms in adult BLs. First, we compared synaptic and extrasynaptic portions of muscle fiber BL, in light of evidence that axonal and muscle membranes interact selectively with synaptic BL during neuromuscular regeneration. S-laminin, laminin A, and collagens alpha 3(IV) and alpha 4(IV) are greatly concentrated in synaptic BL; laminin B1 is apparently absent from synaptic BL; collagens alpha 1(IV) and alpha 2(IV) are less abundant in synaptic than extrasynaptic BL; and laminin B2 and merosin M are present at similar levels synaptically and extrasynaptically. These results reveal widespread differences between synaptic and extrasynaptic BL, and implicate several novel polypeptides as candidate mediators of neuromuscular interactions. Second, we widened our inquiry to assess the composition of several other BLs: endoneurial and perineurial BLs in intramuscular nerves, BLs associated with intramuscular vasculature, and glomerular and tubular BLs in kidney. Of eight BLs studied, at least seven have distinct compositions, and of the nine BL components tested, at least seven have distinct distributions. These results demonstrate a hitherto undescribed degree of heterogeneity among BLs.
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
J R
JR
Sanes
E
E
Engvall
R
R
Butkowski
D D
DD
Hunter
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001485:Basement Membrane / Q000737:chemistry*; D002675:Child, Preschool; D003094:Collagen / Q000032:analysis* / Q000145:classification; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007797:Laminin / Q000032:analysis* / Q000145:classification; D008297:Male; D009121:Muscle Denervation; D009132:Muscles / Q000737:chemistry; D009469:Neuromuscular Junction / Q000737:chemistry*; D011817:Rabbits; D051381:Rats; D013569:Synapses / Q000737:chemistry
D007797:Laminin; D003094:Collagen