AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats.
Ordered differential display identified a novel sequence induced in neurons by the neurite-promoting protein amphoterin. We named this gene amphoterin-induced gene and ORF (AMIGO), and also cloned two other novel genes homologous to AMIGO (AMIGO2 and AMIGO3). Together, these three AMIGOs form a novel family of genes coding for type I transmembrane proteins which contain a signal sequence for secretion and a transmembrane domain. The deduced extracellular parts of the AMIGOs contain six leucine-rich repeats (LRRs) flanked by cysteine-rich LRR NH2- and COOH-terminal domains and by one immunoglobulin domain close to the transmembrane region. A substrate-bound form of the recombinant AMIGO ectodomain promoted prominent neurite extension in hippocampal neurons, and in solution, the same AMIGO ectodomain inhibited fasciculation of neurites. A homophilic and heterophilic binding mechanism is shown between the members of the AMIGO family. Our results suggest that the members of the AMIGO protein family are novel cell adhesion molecules among which AMIGO is specifically expressed on fiber tracts of neuronal tissues and participates in their formation.
Kuja-Panula
Juha
J
Neuroscience Center, Viikinkaari 5, PO Box 56, University of Helsinki, Helsinki 00014, Finland. Juha.Kuja-Panula@Helsinki.fi
Kiiltomäki
Marjaana
M
Yamashiro
Takashi
T
Rouhiainen
Ari
A
Rauvala
Heikki
H
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D022081:Cell Surface Extensions / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005333:Fetus; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D024243:HMGB1 Protein; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D007150:Immunohistochemistry; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000302:isolation & purification*; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
C473888:Amigo1 protein, rat; C473886:Amigo2 protein, rat; C473887:Amigo3 protein, rat; D018076:DNA, Complementary; D024243:HMGB1 Protein; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; D007930:Leucine