Functional Interactions of the Immunoglobulin Superfamily Member F11 Are Differentially Regulated by the Extracellular Matrix Proteins Tenascin-R and Tenascin-C

Abstract

The axon-associated protein F11 is a GPI-anchored member of the immunoglobulin superfamily that promotes axon outgrowth and that shows a complex binding pattern toward multiple cell surface and extracellular matrix proteins including tenascin-R and tenascin-C. In this study, we demonstrate that tenascin-R and tenascin-C differentially modulate cell adhesion and neurite outgrowth of tectal cells on F11. While soluble tenascin-R increases the number of attached cells and the percentage of cells with neurites on immobilized F11, tenascin-C stimulates cell attachment to a similar extent but decreases neurite outgrowth. The cellular receptor interacting with F11 has been previously identified as NrCAM; however, in the presence of tenascin-R or tenascin-C cell attachment and neurite extension are independent of NrCAM. Antibody perturbation experiments indicate that ␤ 1 integrins instead of NrCAM function as receptor for neurite outgrowth of tectal cells on an F11⅐TN-R complex. Cellular binding assays support the possibility that the interaction of F11 to NrCAM is blocked in the presence of tenascin-R and tenascin-C. Furthermore, a sandwich binding assay demonstrates that tenascin-R and tenascin-C are able to form larger molecular complexes and to link F11 polypeptides by forming a molecular bridge.These results suggest that the molecular interactions of F11 might be regulated by the presence of tenascin-R and tenascin-C. Cell adhesion molecules (CAMs)1 of the immunoglobulin superfamily (IgSF) act in concert with other cell surface molecules and extracellular matrix (ECM) proteins to regulate cell migration, axonal growth, and guidance during development of the nervous system. IgSF members coexist on many extending axons and show a transient expression pattern during early stages of development. The multidomain nature of glycoproteins of the IgSF suggest that they regulate axonal pathfinding by multiple complex interactions with other axonal and ECM molecules (1).The axon-associated F11 glycoprotein is composed of six Nterminal Ig domains followed by four fibronectin type III (FNIII) domains and a glycosylphosphatidylinositol anchor and has been implicated in axonal growth and fasciculation (2-6).As found for other axonal members of the IgSF, the F11 polypeptide shows a broad binding activity. Interactions with the cell surface proteins NgCAM, NrCAM, neurofascin, Caspr, and RPTP␤/ and the ECM glycoproteins tenascin-R (TN-R) and tenascin-C (TN-C) have been revealed by in vitro assays (7-16). The N-terminal Ig domains 1-4 of the F11 polypeptide are sufficient for interactions with NgCAM, NrCAM, TN-R, and TN-C, although binding assays with domain-specific anti-F11 monoclonal antibodies and with F11 domain deletion mutants suggest that individual domains of the four N-terminal domains might be more important for specific bindings (8 -10, 15). The interaction between immobilized F11 and neuronal NrCAM induces neurite outgrowth of tectal cells (10). TN-R and TN-C are two major members of the tenascin family of ECM glycoprote...

Radial migration of developing microglial cells in quail retina: A confocal microscopy study

“…However, microglial cells that ramify at L1 can then resume their radial migration to reach L2 (interface between sublayers within the IPL) and L3 (IPL-INL interface) by traversing the tenascinrich territory of the IPL. This would be explained by the presence in the tenascin molecule of domains with opposite functions, adhesive and antiadhesive Norenberg et al, 1995;Faissner, 1997;Ghert et al, 2001), and by the ability of this molecule to bind to different receptors (Schnapp et al, 1995;Mackie, 1997;Zacharias et al, 1999;Pesheva and Probstmeier, 2000). Therefore, tenascin is able to exert both inhibitory and stimulatory effects on cell migration (Faissner, 1997).…”

Regulatory Mechanisms that Mediate Tenascin C-Dependent Inhibition of Oligodendrocyte Precursor Differentiation

“…Tncdependent proliferation of OPCs depends on ␣ v ␤ 3 integrin (Garcion et al, 2001). Tnc also interacts with the cell adhesion molecule (CAM) contactin (Cntn1) (Zacharias et al, 1999;Rigato et al, 2002), which in turn associates with the Src family kinase (SFK) Fyn in lipid rafts (Kramer et al, 1999). Lipid raft formation is necessary for integrin-dependent signaling via phosphatidylinositol-3 kinase (PI3K) to mediate oligodendrocyte survival (Decker and ffrench-Constant, 2004).…”

CALEB Binds via Its Acidic Stretch to the Fibrinogen-like Domain of Tenascin-C or Tenascin-R and Its Expression Is Dynamically Regulated after Optic Nerve Lesion

“…For example, TN-C and TN-R contain both adhesive and counteradhesive sites for cell attachment. TN-C is able to stimulate neurite outgrowth (30), and TN-R has been shown to enhance neurite growth mediated by other substrates and to modulate the cellular receptor usage that is responsible for mediating the outgrowth effect (31,32).…”