Complementary expression and neurite outgrowth activity of netrin-G subfamily members.
Classical members of the UNC6/netrin family are secreted proteins which play a role as long-range cues for directing growth cones. We here identified in mice a novel member netrin-G2 which constitute a subfamily with netrin-G1 among the UNC6/netrin family. Both of these netrin-Gs are characterized by glycosyl phosphatidyl-inositol linkage onto cells, molecular variants presumably generated by alternative splicing and lack of any appreciable affinity to receptors for classical netrins. These genes are preferentially expressed in the central nervous system with complementary distribution in most brain areas, that is netrin-G1 in the dorsal thalamus, olfactory bulb and inferior colliculus, and netrin-G2 in the cerebral cortex, habenular nucleus and superior colliculus. Consistently, immunohistochemical analysis revealed that netrin-G1 molecules are present on thalamocortical but not corticothalamic axons. Thalamic and neocortical neurons extended long neurites on immobilized recombinant netrin-G1 or netrin-G2 in vitro. Immobilized anti-netrin-G1 antibodies altered shapes of cultured thalamic neurons. We propose that netrin-Gs provide short-range cues for axonal and/or dendritic behavior through bi-directional signaling.
Nakashiba
Toshiaki
T
Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan.
Nishimura
Sachiko
S
Ikeda
Toshio
T
Itohara
Shigeyoshi
S
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology / Q000502:physiology*; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D000075386:Netrin Receptors; D000075385:Netrins; D016501:Neurites / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D000075385:Netrins; C456263:Ntng2 protein, mouse; D011956:Receptors, Cell Surface; C413653:netrin-G1