The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Axons, Cerebral Cortex, Chick Embryo, Female, Humans, Ligands, Male, Membrane Proteins, Mice, Molecular Sequence Data, Nerve Tissue Proteins, Protein Binding, Receptors, Cell Surface, Thalamus
Amino Acid Sequence, Animals, Axons, Cerebral Cortex, Chick Embryo, Female, Humans, Ligands, Male, Membrane Proteins, Mice, Molecular Sequence Data, Nerve Tissue Proteins, Protein Binding, Receptors, Cell Surface, Thalamus
Nat. Neurosci.
Date: Dec. 01, 2003
PubMed ID: 14595443
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