LIG family receptor tyrosine kinase-associated proteins modulate growth factor signals during neural development

Neuron. 2009 Sep 10;63(5):614-27. doi: 10.1016/j.neuron.2009.07.031.


Genome-wide screens were performed to identify transmembrane proteins that mediate axonal growth, guidance and target field innervation of somatosensory neurons. One gene, Linx (alias Islr2), encoding a leucine-rich repeat and immunoglobulin (LIG) family protein, is expressed in a subset of developing sensory and motor neurons. Domain and genomic structures of Linx and other LIG family members suggest that they are evolutionarily related to Trk receptor tyrosine kinases (RTKs). Several LIGs, including Linx, are expressed in subsets of somatosensory and motor neurons, and select members interact with TrkA and Ret RTKs. Moreover, axonal projection defects in mice harboring a null mutation in Linx resemble those in mice lacking Ngf, TrkA, and Ret. In addition, Linx modulates NGF-TrkA- and GDNF-GFRalpha1/Ret-mediated axonal extension in cultured sensory and motor neurons, respectively. These findings show that LIGs physically interact with RTKs and modulate their activities to control axonal extension, guidance and branching.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / growth & development
  • Ganglia, Spinal / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Motor Neurons / physiology
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / physiology*
  • Neurotrophin 3 / genetics
  • Neurotrophin 3 / metabolism
  • Peripheral Nervous System / embryology
  • Peripheral Nervous System / growth & development
  • Peripheral Nervous System / metabolism
  • Proto-Oncogene Proteins c-ret / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, trkA / metabolism
  • Receptors, Nerve Growth Factor / metabolism
  • Sensory Receptor Cells / physiology
  • Sequence Analysis, DNA
  • Sequence Homology
  • Spinal Cord / embryology
  • Spinal Cord / growth & development
  • Spinal Cord / metabolism


  • Intercellular Signaling Peptides and Proteins
  • Linx protein, mouse
  • Nerve Tissue Proteins
  • Neurotrophin 3
  • Receptors, Nerve Growth Factor
  • TNFRSF16 protein, mouse
  • Nerve Growth Factor
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Ret protein, mouse