Neuroplastin (NPTN) is a glycoprotein that belongs to the immunoglobulin (Ig) superfamily of cell adhesion molecules (CAMs). Together with basigin/CD147 and embigin, NPTN comprises the CD147 family (Iacono et al. 2007).NPTN isoform p65 binds GABAA receptor subunits, co-localizing with alpha1 and alpha2, but not alpha3 subunits at GABAergic synapses and alpha5 subunits at extrasynaptic sites in cultures (Sarto-Jackson et al. 2012). GABAA receptors containing alpha1, 2 or 3 subunits are localized mainly at synaptic sites and interact with the scaffolding protein Gephyrin (GPHN), which anchors the receptor to the underlying postsynaptic complex and prevents their lateral diffusion (Kneussel & Loebrich 2007, Tretter et al. 2012). Receptors containing the alpha5 subunit are mainly extrasynaptic and link to the actin cytoskeleton via Radixin (Loebrich et al. 2006). NPTN p65 co-localization can be at several synaptic sites along the same dendrite, while absent from others. NPTN p65 shRNA caused diffuse alpha2 subunit staining which did not co-localize with vesicular inhibitory aa transporter, a presynaptic marker of GABAergic synapses (Sarto-Jackson et al. 2012). This suggests a functional role for NPTN p65 in regulating the composition and localization of GABAA receptors (Beesley et al. 2014). The absence of NPTN p65 causes early-onset sensorineural hearing loss and prevents normal synaptogenesis in cochleal inner hair cells (IHCs) (Carrott et al. 2016).
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