Year: 2014
Type: dissertation
Abstract: The purpose for this PhD research is to find a novel gene induced by neurite outgrowth on amphoterin substrate. The finding was a gene that codes type-I transmembrane protein with six leucine-rich repeat (LRR) motifs and one immunoglobulin domain followed by a short cytoplasmic tail. We named this gene as amphoterin-induced gene and ORF (Amigo). Further characterization of AMIGO protein revealed that AMIGO itself is a neurite outgrowth promoting factor and it is also required for the fasciculation of neurites both in vitro and in vivo. The mode of these functions was shown to be homophilic, which puts AMIGO in a group of homophilic cell adhesion molecules. We crystallized the extracellular domain of AMIGO to elucidate the mechanism for its functions. AMIGO crystallized as a homophilic dimer where the concave face of the LRR domain was the interface for dimerization. The isolation of Amigo allowed us to characterize two other homologous genes called Amigo2 and Amigo3 and together they form the novel Amigo gene family. AMIGO protein was found to be an auxiliary subunit of the voltage-gated potassium channel Kv2.1 in adult animals. AMIGO mediates the regulation of the voltage-gating properties of Kv2.1. This AMIGO/Kv2.1 interaction was also studied at the whole animal level by using Amigo knockout mice whereby the lack of Amigo changed voltage-gated potassium currents and resulted in behavioral problems related to human schizophrenia. All these findings suggest that AMIGO has two separate roles in the central nervous system (CNS). First, AMIGO is a homophilic adhesion molecule that supports neurite outgrowth and fasciculation of the neurites during development. Second, the AMIGO regulates the properties of the voltage-gated potassium channel Kv2.1 in the mature CNS.
Source: Työväentutkimus Vuosikirja
Author: Juha Kuja‐Panula
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1516818752