AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats

Abstract

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.

Phenotype–genotype correlation in two patients with 12q proximal deletion

“…Thus, a YAF2 deletion may have caused the growth retardation and/or hypotonicity in the two patients. As AMIGO2 is highly expressed in the nervous system and plays a role in growth of axonal connection and myelination (Kuja-Panula et al 2003); its deletion can cause psychomotor developmental delay.…”

AMIGO2, a novel membrane anchor of PDK1, controls cell survival and angiogenesis via Akt activation

“…The amino acid alignment among the AMI GO family revealed that the binding of the C-terminal region of AMI GO2 to the PH domain of PDK1 is highly conserved, although the amino acid homologies between AMI GO2 and AMI GO1 and between AMI GO2 and AMI GO3 are both 48% (Kuja-Panula et al, 2003). The similarity of the binding sequence to the PH domain indicates that PDK1 is also likely to interact with AMI GO1 and AMI GO3 expressed in a variety of cell types.…”

“…The forward and reverse murine AMI GO2 primers were 5′-GGC ACTTT AGCTC CGTGA TG-3′ and 5′-GTC TCGTT TAACA GCCGC TG-3′, respectively, as previously described (Kuja-Panula et al, 2003). For the mouse GAP DH control, the forward and reverse primers were 5′-CAA CGACC CCTTC ATTGA CC-3′ and 5′-AGT GATGG CATGG ACTGT GG-3′, respectively.…”

“…The adhesion molecule with IgG-like domain (AMI GO) family was identified by ordered differential display, which revealed a novel sequence induced by amphoterin, the neurite outgrowth-promoting factor in neurons (Kuja-Panula et al, 2003). AMI GO2 promotes the depolarization-dependent survival of cerebellar granule neurons (Ono et al, 2003).…”

“…Furthermore, the stable expression of antisense AMI GO2 in gastric adenocarcinoma cell lines leads to abrogated tumorigenicity (Rabenau et al, 2004). AMI GO2 contains six leucine-rich repeats (LRRs), a single IgG-like domain, a transmembrane domain, and a cytosolic domain (CD; Kuja-Panula et al, 2003;Chen et al, 2006). An algorithm analysis suggested that the CD of AMI GO2 might provide a docking site for signaling pathway intermediates, thereby making it an important participant in signal transduction (Rabenau et al, 2004).…”