About this Research Topic
L-glutamate is a non-essential amino acid that plays a pivotal role in the nervous system, primarily acting through ionotropic glutamate receptors (iGluRs) mediating the bast majority of rapid excitatory synaptic transmission. iGluRs, are tetrameric receptors that can be classified in four distinct subtypes, including delta-receptors. The three primary and extensively studied iGluRs are named based on compounds that selectively activate them: N-methyl-D-aspartate (NMDA) receptors (NMDARs), α-amino-3-hydroxy-5-methyl4-isoxazole propionate (AMPA) receptors (AMPARs), and kainate (KA) receptors (KARs). The ability to combine different subunits results in the formation of homo and heterotetrametric receptors, leading to a large diversity of iGluRs with distinct biophysical properties and, consequently, diverse signaling mediated by L-glutamate.
Beyond the various combinations of core pore-forming subunits, it is now well-established that AMPARs and KARs can form functional receptors in conjunction with various auxiliary subunits. These auxiliary subunits play a direct role in modulating receptor function and biophysical properties. Indirectly, the diverse combinations of auxiliary subunits contribute to the functional diversity of KARs and AMPARs, offering the potential to finely tune neuron-to-neuron signaling.
To date, several families of auxiliary proteins have been identified as regulators of AMPARs and KARs. Members of the claudin family, various Transmembrane Regulatory AMPA Receptors Proteins (TARP), and GSG1L (germ cell-specific gene 1-like) are crucial in modulating AMPAR function. Additionally, auxiliary proteins such as cornichons 2 and 3 (CNIH-2 and 3), the CKAMP family, and SynDIG have been discovered to regulate AMPAR biophysical properties. Furthermore, the biosynthesis of the AMPAR complex, including auxiliary subunits, appears to be finely regulated by other proteins like FRRS1L, CPT1-C, or ABH6D, among others. On the other hand, although only two proteins, Neto-1 and 2, have been identified as KAR auxiliary subunits to date but this number may be an underestimate.
Collectively, this complexity adds to our understanding of glutamatergic signaling. Different research groups have characterized the properties of various AMPAR and KAR complexes in both native and recombinant receptors. Nevertheless, there remains a significant amount of work to be done to fully comprehend the molecular and structural foundations and mechanisms of AMPAR and KAR biology, including how other proteins regulate the function of these receptors in both physiological and pathological conditions.
To contribute to the dissemination of the latest advancements in ongoing on the function and understanding of iGluRs, the editors propose the present Research Topic, where review articles, original research, and reports covering the most recent research in the field will be published.
The main interests for this Research Topic may involve:
- Mechanistic work done on iGluR-auxiliary proteins interaction.
- Extended functional study of auxiliary proteins that modulate iGluRs.
- Structural work on how auxiliary subunits regulate iGluRs.
Beyond the various combinations of core pore-forming subunits, it is now well-established that AMPARs and KARs can form functional receptors in conjunction with various auxiliary subunits. These auxiliary subunits play a direct role in modulating receptor function and biophysical properties. Indirectly, the diverse combinations of auxiliary subunits contribute to the functional diversity of KARs and AMPARs, offering the potential to finely tune neuron-to-neuron signaling.
To date, several families of auxiliary proteins have been identified as regulators of AMPARs and KARs. Members of the claudin family, various Transmembrane Regulatory AMPA Receptors Proteins (TARP), and GSG1L (germ cell-specific gene 1-like) are crucial in modulating AMPAR function. Additionally, auxiliary proteins such as cornichons 2 and 3 (CNIH-2 and 3), the CKAMP family, and SynDIG have been discovered to regulate AMPAR biophysical properties. Furthermore, the biosynthesis of the AMPAR complex, including auxiliary subunits, appears to be finely regulated by other proteins like FRRS1L, CPT1-C, or ABH6D, among others. On the other hand, although only two proteins, Neto-1 and 2, have been identified as KAR auxiliary subunits to date but this number may be an underestimate.
Collectively, this complexity adds to our understanding of glutamatergic signaling. Different research groups have characterized the properties of various AMPAR and KAR complexes in both native and recombinant receptors. Nevertheless, there remains a significant amount of work to be done to fully comprehend the molecular and structural foundations and mechanisms of AMPAR and KAR biology, including how other proteins regulate the function of these receptors in both physiological and pathological conditions.
To contribute to the dissemination of the latest advancements in ongoing on the function and understanding of iGluRs, the editors propose the present Research Topic, where review articles, original research, and reports covering the most recent research in the field will be published.
The main interests for this Research Topic may involve:
- Mechanistic work done on iGluR-auxiliary proteins interaction.
- Extended functional study of auxiliary proteins that modulate iGluRs.
- Structural work on how auxiliary subunits regulate iGluRs.
Keywords: iGlur, NMDA, AMPARs, AMPA, KARs
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