GluD receptors are functional ion channels

Abstract

In this article, we review contemporary evidence that GluD receptors are functional ion channels whose depolarizing currents contribute to their biological functions, akin to all other members of the ionotropic glutamate receptor (iGluR) family.

Figure 1

Phylogeny and shared layered structural domains of the iGluR family. (A) Phylogenic tree of the human genes encoding for 18 different iGluR subunits with percent shared sequence identity. (B) Cartoon of the membrane topology of one iGluR subunit showing the extracellular bi-lobed N-terminal (ATD) and ligand binding (LBD) domains, the three membrane-spanning helices and a re-entrant P loop (TMD), and an intracellular C-terminal domain (CTD). Four subunits assemble to form a functional ion channel.

Figure 2

GluD1 and AtGLR3.4 share a nonswapped conformation. (A) Side views of GluD1 (6KSS), AtGLR3.4 (7LZH), and GluA2 (5KBV) receptors, illustrating their Y-shaped structure, are shown. Each subunit in the receptor tetramer is represented by a unique color. (B) Top views of GluD1, AtGLR3.4, and GluA2 for their ATD, LBD, and TMD domains highlighting the subunit arrangement and the lack of domain swapping between the ATD and LBD layer in GluD1 and AtGLY3.4 unlike that in GluA2 receptors. To see this figure in color, go online.

Figure 3

GluD receptors are functional cation channels that when activated, carry excitatory current and promote action potential firing. (A) GluD may be gated directly by glycine or D-serine when mechanically stabilized by formation of the neurexin-cerebellin-GluD trans-synaptic complex, spanning ∼16 nm. GluD receptors also pass current in response to Gαq protein-coupled receptor activation, but the second messenger signal has not yet been identified. To see this figure in color, go online.