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.
Lin
John C
JC
Rinat Neuroscience Corporation, 3155 Porter Drive, Palo Alto, California 94304, USA.
Ho
Wei-Hsien
WH
Gurney
Austin
A
Rosenthal
Arnon
A
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism*; D002642:Chick Embryo; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000075386:Netrin Receptors; D000075385:Netrins; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D013788:Thalamus / Q000196:embryology / Q000378:metabolism*
C480698:LRRC4C protein, human; D008024:Ligands; D008565:Membrane Proteins; C000594607:NGL1 protein, mouse; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D000075385:Netrins; D011956:Receptors, Cell Surface; C413653:netrin-G1