Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons.

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Spanaki C, Kotzamani D, Kleopa K, Plaitakis A

Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons.

Mol Neurobiol. 2016 Oct;53(8):5140-8. doi: 10.1007/s12035-015-9429-2. Epub 2015 Sep 23.

PubMed ID

26399640 [ View in PubMed

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Abstract

Human hGDH2 arose via duplication in the apes and driven by positive selection acquired enhanced catalytic ability under conditions inhibitory to its precursor hGDH1 (common to all mammals). To explore the biological advantage provided by the novel enzyme, we studied, by immunohistochemistry (IHC) and immunofluorescence (IF), hGDH1 and hGDH2 expression in the human brain. Studies on human cortical tissue using anti-hGDH1-specific antibody revealed that hGDH1 was expressed in glial cells (astrocytes, oligodendrocytes, and oligodendrocyte precursors) with neurons being devoid of hGDH1 staining. In contrast, an hGDH2-specific antiserum labeled both astrocytes and neurons. Specifically, hGDH2 immunoreactivity was found in the cytoplasm of large neuronal cells within coarse structures resembling mitochondria. These were distributed either in the perikaryon or in the cell periphery. Double immunofluorescence (IF) suggested that the latter represented hGDH2-labeled mitochondria of presynaptic nerve terminals. Hence, hGDH2 evolution bestowed large human neurons with enhanced glutamate metabolizing capacity, thus strengthening cortical excitatory transmission.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutamic acid	Glutamate dehydrogenase 2, mitochondrial	Protein	Humans	Unknown	Substrate	Details