Binding of mouse nidogen-2 to basement membrane components and cells and its expression in embryonic and adult tissues suggest complementary functions of the two nidogens.
Nidogen-1 binds several basement membrane components by well-defined, domain-specific interactions. Organ culture and gene targeting approaches suggest that a high-affinity nidogen-binding site of the laminin gamma1 chain (gamma1III4) is important for kidney development and for nerve guidance. Other proteins may also bind gamma1III4, although human nidogen-2 binds poorly to the mouse laminin gamma1 chain. We therefore characterized recombinant mouse nidogen-2 and its binding to basement membrane proteins and cells. Mouse nidogen-1 and -2 interacted at comparable levels with collagen IV, perlecan, and fibulin-2 and, most notably, also with laminin-1 fragments P1 and gamma1III3-5, which both contain the gamma1III4 module. In embryos, nidogen-2 mRNA was produced by mesenchyme at sites of epithelial-mesenchymal interactions, but the protein was deposited on epithelial basement membranes, as previously shown for nidogen-1. Hence, binding of both nidogens to the epithelial laminin gamma1 chain is dependent on epithelial-mesenchymal interactions. Epidermal growth factor stimulated expression of both nidogens in embryonic submandibular glands. Both nidogens were found in all studied embryonic and adult basement membranes. Nidogen-2 was more adhesive than nidogen-1 for some cell lines and was mainly mediated by alpha3beta1 and alpha6beta1 integrins as shown by antibody inhibition. These findings revealed extensive coregulation of nidogen-1 and -2 expression and much more complementary functions of the two nidogens than previously recognized.
Salmivirta
Katriina
K
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Talts
Jan F
JF
Olsson
Magnus
M
Sasaki
Takako
T
Timpl
Rupert
R
Ekblom
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001485:Basement Membrane / Q000737:chemistry / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014018:Tissue Distribution; D019096:Vitronectin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D019812:Heparan Sulfate Proteoglycans; D016023:Integrins; D007797:Laminin; D008562:Membrane Glycoproteins; C114729:NID2 protein, human; D011994:Recombinant Proteins; D019096:Vitronectin; C060820:fibulin; C029967:nidogen; C071927:perlecan