The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons

• Published in: Nature neuroscience Vol. 6; no. 12; pp. 1270 - 1276
• Main Authors: Lin, John C, Rosenthal, Arnon, Ho, Wei-Hsien, Gurney, Austin
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2003
• Subjects: Amino Acid Sequence - physiology; Animals; Axons; Axons - metabolism; Central nervous system; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; Chick Embryo; Female; Humans; Ligands; Male; Membrane proteins; Membrane Proteins - metabolism; Membrane Proteins - physiology; Mice; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Netrin Receptors; Netrins; Physiological aspects; Protein Binding - drug effects; Protein Binding - physiology; Proteins; Receptors, Cell Surface - metabolism; Receptors, Cell Surface - physiology; Thalamus - embryology; Thalamus - metabolism; United States; United States > US; California
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn1148

Netrin-G1 is a lipid-anchored protein that is structurally related to the netrin family of axon guidance molecules. Netrin-G1 does not bind any of the known netrin receptors and its function is not known. Here we identify human netrin-G1 ligand (NGL-1), a transmembrane protein containing leucine-rich repeat (LRR) and immunoglobulin (Ig) domains that specifically interacts with netrin-G1 through its LRR region. Whereas netrin-G1 is expressed highly in mouse thalamic axons, NGL-1 is most abundant in the striatum and the cerebral cortex--the intermediate and final targets, respectively, of thalamocortical axons (TCAs). Surface-bound NGL-1 stimulates, but soluble NGL-1 disrupts, the growth of embryonic thalamic axons, and in vitro data indicate that NGL-1 activity may be mediated at least partially by netrin-G1. Our findings provide evidence that netrin-G1 functions as an important component of the NGL-1 receptor to promote TCA outgrowth and that membrane-bound netrins can participate in receiving axonal signaling pathways.