New insights into the structure and function of glutamate receptors : orphan receptor δ2 reveals its family's secrets

スポンサーリンク

概要

• 論文の詳細を見る

• The ionotropic glutamate receptors (iGluRs) form ligand-gated ion channels that mediate the vast majority of excitatory neurotransmission in the mammalian brain. These receptors play central roles not only in normal neurodevelopmental and neurophysiological processes but also in certain neuropathological processes. Molecular cloning of genes for iGluRs in the past decade has advanced our understanding of the basic properties of iGluRs, such as ion selectivity, ligand binding, and anchoring at synapses. Although the gene for the δ2 glutamate receptor (GluRδ2) was cloned on the basis of homology screening, GluRδ2 has been referred to as an “orphan” receptor because it does not form functional glutamate-gated ion channels. However, ataxia in many types of mice is caused by spontaneous mutation of GluRδ2. Analysis of two such mutants, lurcher and hotfoot, has provided key insights into the GluRδ2 signaling in neurons. Furthermore, characterization of mutant GluRδ2 has revealed unexpected clues to two fundamental features regarding the structure and function of iGluRs gating and assembly. Studies have recently shown that the transmembrane region where the lurcher mutation is located probably plays a crucial role in channel gating. The mechanism that controls iGluR subunit assembly seems to involve the extracellular N-terminal domain where the hotfoot mutation is located. An understanding of mechanisms responsible for gating and assembly is essential for the comprehension of neuronal function and dysfunction. Although reverse genetics is useful in deciphering glutamate signaling, these findings demonstrate the power of classic approaches to forward genetics on mutant mice.

• The Keio Journal of Medicineの論文
• 2003-06-01

著者

• Yuzaki Michisuke

  Department Of Biochemistry Jichi Medical School:(present Address) Dept. Of Developmental Neurobiolog

• Yuzaki Michisuke

  Department Of Developmental Neurology St. Jude Children's Research Hospital

関連論文

• Potential functional neural repair with grafted neural stem cells of early embryonic neuroepithelial origin
• An Additional Form of Rat Bcl-x, Bcl-xβ, Generated by an Unspliced RNA, Promotes Apoptosis in Promyeloid Cells
• Phosphorylation of Delta2 Glutamate Receptors at Serine 945 is Not Required for Cerebellar Long-term Depression
• Polarized sorting of AMPA receptors of the somatodendritic domain is regulated by adaptor protein AP-4
• The δ2 glutamate receptor : 10 years later
• New insights into the structure and function of glutamate receptors : orphan receptor δ2 reveals its family's secrets

スポンサーリンク