Neurite Fasciculation Mediated by Complexes of Axonin-1 and Ng Cell Adhesion Molecule

Abstract

Neural cell adhesion molecules composed of immunoglobulin and fibronectin type III-like domains have been implicated in cell adhesion, neurite outgrowth, and fasciculation. Axonin-1 and Ng cell adhesion molecule (NgCAM), two molecules with predominantly axonal expression exhibit homophilic interactions across the extracellular space (axonin- 1/axonin-1 and NgCAM/NgCAM) and a heterophilic interaction (axonin-1–NgCAM) that occurs exclusively in the plane of the same membrane (cis-interaction). Using domain deletion mutants we localized the NgCAM homophilic binding in the Ig domains 1-4 whereas heterophilic binding to axonin-1 was localized in the Ig domains 2-4 and the third FnIII domain. The NgCAM–NgCAM interaction could be established simultaneously with the axonin-1–NgCAM interaction. In contrast, the axonin-1–NgCAM interaction excluded axonin-1/axonin-1 binding. These results and the examination of the coclustering of axonin-1 and NgCAM at cell contacts, suggest that intercellular contact is mediated by a symmetric axonin-12/NgCAM2 tetramer, in which homophilic NgCAM binding across the extracellular space occurs simultaneously with a cis-heterophilic interaction of axonin-1 and NgCAM. The enhanced neurite fasciculation after overexpression of NgCAM by adenoviral vectors indicates that NgCAM is the limiting component for the formation of the axonin-12/NgCAM2 complexes and, thus, neurite fasciculation in DRG neurons.

Lewisxand α2,3-Sialyl Glycans and Their Receptors TAG-1, Contactin, and L1 Mediate CD24-Dependent Neurite Outgrowth

“…A functional heterophilic interaction of L1 with TAG-1 has been shown by colocalization on DRG neurons (Kuhn et al, 1991) and coimmunoprecipitation from cells cotransfected with the two molecules (Kunz et al, 1998;Malhotra et al, 1998) or from DRG neurons (Buchstaller et al, 1996). Other reports have also documented an interaction of Contactin and L1 (Brüm-mendorf et al, 1993;Olive et al, 1995).…”

Topographic Restriction of TAG-1 Expression in the Developing Retinotectal Pathway and Target Dependent Reexpression during Axon Regeneration

“…TAG-1 confers positiondependent identity and may control the developing spatial organization of nasal axons. To which extent such functions require homophilic and/or heterophilic interactions of TAG-1 with L1 (Rader et al, 1993;Kunz et al, 1998) or the L1-related E587 antigen (Giordano et al, 1997) or with other axonally expressed molecules remains to be examined. TAG-1 not only occurs in its GPI-anchored form on the axonal surface but also exists as a soluble protein in the vitreous which apparently binds to intraretinal axons (as well as to cellular processes of unknown identity).…”

“…It is conceivable that it affects axon growth and/or integrity of the tissue. Such may result from the complex interactions that TAG-1/ axonin-1 exhibits: e.g., with L1/NgCAM, NrCAM, neurocan, and phosphacan/protein-phosphatase ␤ (in Kunz et al, 1998). The cellular processes may possess TAG-1 binding proteins which differ from those present on the RGC axons because staining of the processes is and remains more intense than that of the temporal axons and than that of the nasal axons after PI-PLC treatment.…”

The SALM Family of Adhesion-like Molecules Forms Heteromeric and Homomeric Complexes

“…For example, the L1 chick homolog NgCAM forms homophilic trans interactions across the extracellular space through its N-terminal Ig domains 1-4, but also forms a heteromeric cis complex with axonin-1 through its Ig domains 2-4 and the third FNIII domain (60). This interaction prevents the formation of trans axonin-1/axonin-1 associations (60,61), and enhances neurite fasciculation (60,62). Another example of cis interactions regulating trans associations includes the neurexins, which were recently reported to be postsynaptic, in addition to being presynaptic (63).…”