TY - JOUR
T1 - LIG Family Receptor Tyrosine Kinase-Associated Proteins Modulate Growth Factor Signals during Neural Development
AU - Mandai, Kenji
AU - Guo, Ting
AU - St. Hillaire, Coryse
AU - Meabon, James S.
AU - Kanning, Kevin C.
AU - Bothwell, Mark
AU - Ginty, David D.
PY - 2009/9/10
Y1 - 2009/9/10
N2 - 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-GFRα1/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.
AB - 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-GFRα1/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.
KW - DEVBIO
KW - MOLNEURO
KW - SIGNALING
UR - http://www.scopus.com/inward/record.url?scp=69949102901&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69949102901&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2009.07.031
DO - 10.1016/j.neuron.2009.07.031
M3 - Article
C2 - 19755105
AN - SCOPUS:69949102901
SN - 0896-6273
VL - 63
SP - 614
EP - 627
JO - Neuron
JF - Neuron
IS - 5
ER -