Beta 8 integrins mediate interactions of chick sensory neurons with laminin-1, collagen IV, and fibronectin.
Integrins are major receptors used by cells to interact with extracellular matrices. In this paper, we identify the first ligands for the beta 8 family of integrins, presenting evidence that integrin heterodimers containing the beta 8 subunit mediate interactions of chick sensory neurons with laminin-1, collagen IV, and fibronectin. A polyclonal antibody, anti-beta 8-Ex, was prepared to a bacterial fusion protein expressing an extracellular portion of the chicken beta 8 subunit. In nonreducing conditions, this antibody immunoprecipitated from surface-labeled embryonic dorsal root ganglia neurons a M(r) 100 k protein, the expected M(r) of the beta 8 subunit, and putative alpha subunit(s) of M(r) 120 k. Affinity-purified anti-beta 8-Ex strongly inhibited sensory neurite outgrowth on laminin-1, collagen IV, and fibronectin-coated substrata. Binding sites were identified in a heat-resistant domain in laminin-1 and in the carboxyl terminal, 40-kDa fibronectin fragment. On substrates coated with the carboxyl terminal fragment of fibronectin, antibodies to beta 1 and beta 8 were only partially effective alone, but were completely effective in combination, at inhibiting neurite outgrowth. Results thus indicate that the integrin beta 8 subunit in association with one or more alpha subunits forms an important set of extracellular matrix receptors on sensory neurons.
Venstrom
K
K
Department of Physiology, University of California San Francisco 94143, USA.
Reichardt
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D006023:Glycoproteins / Q000494:pharmacology; D039641:Integrin beta Chains; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007797:Laminin / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D009433:Neural Inhibition / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013379:Substrate Specificity / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D019063:Tenascin; D019096:Vitronectin
D000906:Antibodies; D015816:Cell Adhesion Molecules, Neuronal; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D006023:Glycoproteins; D039641:Integrin beta Chains; D016023:Integrins; D007797:Laminin; D008024:Ligands; D019063:Tenascin; D019096:Vitronectin; C094865:integrin beta8; D003094:Collagen