AMIGO is expressed in multiple brain cell types and may regulate dendritic growth and neuronal survival

Abstract

Amphoterin-induced gene and ORF (AMIGO) is a brain-enriched transmembrane immunoglobulin (Ig) superfamily protein with six extracellular leucine-rich repeats (LRR) and a single immunoglobulin-like (Ig) domain. We report here that AMIGO is a glycosylated protein widely expressed in the central nervous system (CNS), and can be found in neurons, astrocytes as well as oligodendrocytes. In morphologically mature primary neurons, endogenous AMIGO, and transfected full length AMIGO (AMIGO-FL) are largely dendritic, while AMIGO with its LRR domain deleted (AMIGO-Ig) is predominantly axonal. In line with AMIGO's dendritic localization, siRNA-mediated silencing of AMIGO resulted in reduced dendritic growth of cortical neurons in culture. SH-SY5Y cells stably over-expressing AMIGO are more resistant to apoptosis induced by staurosporine and H(2) O(2) compared to vector controls. AMIGO therefore likely plays important roles in dendritic outgrowth during development, and could modulate the survival of developing and adult neurons.

Amigo Adhesion Protein Regulates Development of Neural Circuits in Zebrafish Brain

“…In 5-dpf zebrafish larvae, Amigo1 expression is found in most brain areas that already have functionally active neural circuits. This finding also resembles the situation in rodents, in which AMIGO1 expression is increased in postnatal brain during construction of the adult-type circuitry and is found in practically all areas of the CNS in most neurons and their fibers in young adults (4,7,9). Such a conserved spatiotemporal expression pattern in vertebrates suggests a conserved function in the CNS development.…”

“…The crystal structure of the AMIGO1 dimer has recently revealed that homophilic binding of AMIGO1 occurs through its LRR domains (8). In addition, AMIGO1 and AMIGO2 (also designated as Alivin1) have been reported to enhance survival of neurons in culture (9,10). Furthermore, AMIGO1 has recently been found to bind to the Kv2.1 potassium channel and to affect excitability of central neurons via the Kv2.1 interactions (11).…”

Lrig1 is a cell‐intrinsic modulator of hippocampal dendrite complexity and BDNF signaling

“…Recent studies provide compelling evidence that transmembrane proteins containing extracellular leucine-rich repeat (LRR) domains control neuronal connectivity functioning as regulators of axon guidance, dendritic growth, synapse formation, and plasticity [15][16][17]. Distinct LRR protein families are highly enriched in the CNS, especially in the hippocampus, where they play a critical role in organizing synaptic connections into functional neural circuits.…”

Neural Cell Adhesion Molecules Belonging to the Family of Leucine-Rich Repeat Proteins

“…However, recently it has been reported that AMIGO1 is also expressed in astroglia and oligodendroglia and that the protein in neurons localizes mainly to dendrites but not axons. Interestingly, an AMIGO1 mutant lacking the LRR domain is mis-allocated to axons rather than dendrites and is transported to the cell surface faster than wild-type AMIGO1 or an AMIGO1 mutant lacking the Ig module (see below) (Chen et al 2012 ).…”

“…They are composed of a ~400 amino acids long ectodomain consisting of six N-terminal LRRs with NF and CF domains, and a membrane-proximal Ig module, a transmembrane domain, and a ~100 amino acids long short cytoplasmic domain (Kuja-Panula et al 2003 ;Ono et al 2003 ;Chen et al 2012 ). The ectodomain of AMIGO1 contains fi ve sites for N-linked glycosylation: two in the LRR domain and three in the Ig module.…”