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The Journal of Neuroscience, November 15, 1998, 18(22):9312-9325

Neurotrimin Mediates Bifunctional Effects on Neurite Outgrowth via Homophilic and Heterophilic Interactions

Orlando D. Gil¹, George Zanazzi¹, Arie F. Struyk¹, and James L. Salzer^{1, 2}

Departments of ¹ Cell Biology and ² Neurology, New York University Medical School, New York, New York 10016

Neurotrimin (Ntm) together with the limbic system-associated membrane protein (LAMP) and the opioid-binding cell adhesion molecule (OBCAM) comprise the IgLON family of neural cell adhesion molecules. These glycosylphosphatidylinositol (GPI)-anchored proteins are expressed in distinct neuronal systems. In the case of Ntm, its expression pattern suggests a role in the development of thalamocortical and pontocerebellar projections (). We have now characterized Ntm's function in cell adhesion and in neurite outgrowth. Cross-linking studies of transfected cells show that Ntm forms noncovalent homodimers and multimers at the cell surface. Ntm mediates homophilic adhesion, as evidenced by the reaggregation of the transfected cells and the specific binding of an Ntm-Fc chimera to these cells. Consistent with these results, Ntm-Fc binds to neurons that express Ntm at high levels, e.g., dorsal root ganglion (DRG) and hippocampal neurons. It does not bind to DRG neurons treated with phosphatidylinositol-specific phospholipase C (PI-PLC) or to sympathetic neurons that do not express Ntm or other members of the IgLON family at significant levels. Ntm promotes the outgrowth of DRG neurons, even after PI-PLC treatment, suggesting that its effects on outgrowth are mediated by heterophilic interactions. Of particular note, both membrane-bound and soluble Ntm inhibit the outgrowth of sympathetic neurons. These results strongly suggest that Ntm, and other members of the IgLON family, regulate the development of neuronal projections via attractive and repulsive mechanisms that are cell type specific and are mediated by homophilic and heterophilic interactions.

Key words: neurotrimin; IgLON family; neurite outgrowth; homophilic adhesion; repulsion; GPI-anchored

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18229312-14$05.00/0

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