Neuropilin and tolloid-like protein 1 (Neto1) and 2 (Neto2) share an identical and unique domain structure representing a new subfamily of transmembrane proteins containing CUB (complement C1r/C1s, Uegf, Bmp1) and LDLa (low-density lipoprotein receptor class A) domains []. Neto1 and Neto2 display a complementary expression profile in the mouse brain [, ]. Fast excitatory synaptic transmission in the vertebrate brain is mediated by three classes of ionotropic glutamate receptors: AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs), NMDA (N-methyl-d-aspartate) receptors (NMDARs), and kainate receptors (KARs). Neto1 and Neto2 auxiliary subunits associate with kainate receptors (KARs) to modulate its function [, ]. Some studies also show that Neto1 and Neto2 associate with NMDA receptors (NMDARs) [, ], while one study does not []. Neto1 is required for synaptic plasticity and learning []. In mice, it is highly expressed in the hippocampal CA3 region, olfactory bulb and tubercle, caudate putamen, and neocortex in the adult brain [, , ].
Neuropilin and tolloid-like protein 1 (Neto1) and 2 (Neto2) share an identical and unique domain structure representing a new subfamily of transmembrane proteins containing CUB (complement C1r/C1s, Uegf, Bmp1) and LDLa (low-density lipoprotein receptor class A) domains []. Neto1 and Neto2 display a complementary expression profile in the mouse brain [, ]. Fast excitatory synaptic transmission in the vertebrate brain is mediated by three classes of ionotropic glutamate receptors: AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs), NMDA (N-methyl-d-aspartate) receptors (NMDARs), and kainate receptors (KARs). Neto1 and Neto2 auxiliary subunits associate with kainate receptors (KARs) to modulate its function [, ]. Some studies also show that Neto1 and Neto2 associate with NMDA receptors (NMDARs) [, ], while one study does not []. Neto2 increases kainate-receptor channel activity, slowing the decay kinetics of the receptors [].
