title: Tenascin-contactin/F11 interactions: a clue for a developmental role?
abstract: To understand how the extracellular matrix glycoprotein tenascin modifies cell adhesion and neurite outgrowth, we sought to isolate cellular receptors for tenascin. So far, two completely different cell surface ligands for tenascin have been detected. This we achieved by affinity chromatography of tissue extracts and of isolated proteins over tenascin-Sepharose and by solid-phase assays using the individual proteins. The first receptor, the neuronal cell adhesion molecule contactin/F11, a member of the immunoglobulin superfamily, binds to tenascin via a site in the N-terminal immunoglobulin-like domains. The binding site is within the fibronectin type III homology region at the boundary of the alternatively spliced region of tenascin, requiring that fibronectin type III homology domains 5 and 9 be adjacent, as they are in the 190 kD tenascin isoform. The close similarity in tertiary structure between type III domains and immunoglobulin-like repeats raises the possibility that we are observing a side-by-side interaction between the two molecules in a manner closely analogous to that between paired immunoglobulin domains. The second receptor is the heparan sulfate proteoglycan, glypican, which, similarly to contactin/F11, is anchored to the membrane via glycosylphosphatidylinositol. Glypican bound to a column of tenascin-Sepharose cannot be dissociated by chondroitin sulfate or dermatan sulfate, but elutes in a broad peak with a gradient of heparan sulfate and in a sharper peak with heparin. By means of fusion proteins, we have identified a potential binding site on the fifth fibronectin type III homology domain of tenascin. We are trying to define these sites more closely by means of site-directed mutagenesis. It will be interesting to see whether the interaction between tenascin and cell surface contactin/F11, and possibly cellular heparan sulfate proteoglycans, contributes to the prominent role played by tenascin in pattern formation during development of the nervous system. In a first step, we have examined the distribution of tenascin isoforms and contactin/F11 during retinal development by means of immunohistochemistry and in situ hybridization with tenascin isoform-specific probes. Tenascin isoforms 190/200 along with contactin/F11 are particularly prominent in the inner and outer plexiform layers of embryonic day 8 retina in the chick. This coordinate up-regulation was confirmed both by immunoblots and Northern blots of retinal extracts. A speculative model is presented to suggest how the unique hexabrachion may signal the cell via contactin/F11.
authors.affiliation: Laboratorium für Biochemie I, ETH-Zentrum, Zürich, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Vaughan
authors.forename: P
authors.initials: P
authors.lastname: Weber
authors.forename: L
authors.initials: L
authors.lastname: D'Alessandri
authors.forename: A H
authors.initials: AH
authors.lastname: Zisch
authors.forename: K H
authors.initials: KH
authors.lastname: Winterhalter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000502:physiology*; D002642:Chick Embryo; D016384:Consensus Sequence; D058966:Contactins; D006224:Cricetinae; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000502:physiology*; D005136:Eye Proteins / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules; D016501:Neurites / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D019063:Tenascin
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D019063:Tenascin