Evolution of NMDA receptor cytoplasmic interaction domains: implications for organisation of synaptic signalling complexes

BMC Neuroscience
Tomás J RyanNoboru H Komiyama

Abstract

Glutamate gated postsynaptic receptors in the central nervous system (CNS) are essential for environmentally stimulated behaviours including learning and memory in both invertebrates and vertebrates. Though their genetics, biochemistry, physiology, and role in behaviour have been intensely studied in vitro and in vivo, their molecular evolution and structural aspects remain poorly understood. To understand how these receptors have evolved different physiological requirements we have investigated the molecular evolution of glutamate gated receptors and ion channels, in particular the N-methyl-D-aspartate (NMDA) receptor, which is essential for higher cognitive function. Studies of rodent NMDA receptors show that the C-terminal intracellular domain forms a signalling complex with enzymes and scaffold proteins, which is important for neuronal and behavioural plasticity The vertebrate NMDA receptor was found to have subunits with C-terminal domains up to 500 amino acids longer than invertebrates. This extension was specific to the NR2 subunit and occurred before the duplication and subsequent divergence of NR2 in the vertebrate lineage. The shorter invertebrate C-terminus lacked vertebrate protein interaction motifs involved with f...Continue Reading

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Methods Mentioned

BETA
in silico methods
protein folding
X-ray
nuclear magnetic resonance

Software Mentioned

TMHMM
Dotmatcher
BLAST
tBLASTn
Ensembl
Ensembl BioMart
PSIPRED
ClustalW
EMBOSS package
FoldIndex

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