| First Author | Bishop HI | Year | 2018 |
| Journal | Front Mol Neurosci | Volume | 11 |
| Pages | 1 | PubMed ID | 29403353 |
| Mgi Jnum | J:267643 | Mgi Id | MGI:6268872 |
| Doi | 10.3389/fnmol.2018.00001 | Citation | Bishop HI, et al. (2018) Kv2 Ion Channels Determine the Expression and Localization of the Associated AMIGO-1 Cell Adhesion Molecule in Adult Brain Neurons. Front Mol Neurosci 11:1 |
| abstractText | Voltage-gated K(+) (Kv) channels play important roles in regulating neuronal excitability. Kv channels comprise four principal alpha subunits, and transmembrane and/or cytoplasmic auxiliary subunits that modify diverse aspects of channel function. AMIGO-1, which mediates homophilic cell adhesion underlying neurite outgrowth and fasciculation during development, has recently been shown to be an auxiliary subunit of adult brain Kv2.1-containing Kv channels. We show that AMIGO-1 is extensively colocalized with both Kv2.1 and its paralog Kv2.2 in brain neurons across diverse mammals, and that in adult brain, there is no apparent population of AMIGO-1 outside of that colocalized with these Kv2 alpha subunits. AMIGO-1 is coclustered with Kv2 alpha subunits at specific plasma membrane (PM) sites associated with hypolemmal subsurface cisternae at neuronal ER:PM junctions. This distinct PM clustering of AMIGO-1 is not observed in brain neurons of mice lacking Kv2 alpha subunit expression. Moreover, in heterologous cells, coexpression of either Kv2.1 or Kv2.2 is sufficient to drive clustering of the otherwise uniformly expressed AMIGO-1. Kv2 alpha subunit coexpression also increases biosynthetic intracellular trafficking and PM expression of AMIGO-1 in heterologous cells, and analyses of Kv2.1 and Kv2.2 knockout mice show selective loss of AMIGO-1 expression and localization in neurons lacking the respective Kv2 alpha subunit. Together, these data suggest that in mammalian brain neurons, AMIGO-1 is exclusively associated with Kv2 alpha subunits, and that Kv2 alpha subunits are obligatory in determining the correct pattern of AMIGO-1 expression, PM trafficking and clustering. |
