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Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons

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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.

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Acknowledgments

This work was supported by the European Union (European Social Fund—ESF) and Greek national funds through the operational program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF)—Research Funding Program: THALIS—UOA, title of grant “Mechanisms of pathogenesis of Parkinson’s disease”, grant code 70/3/11679.

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Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Crete, Heraklion, Crete, Greece

    Cleanthe Spanaki, Dimitra Kotzamani & Andreas Plaitakis

  2. Neuroscience Laboratory and Neurology Clinics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

    Kleopas Kleopa

  3. Faculty of Medicine, School of Health Sciences, University of Crete, Voutes, 71003, Heraklion, Crete, Greece

    Cleanthe Spanaki

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  1. Cleanthe Spanaki
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  2. Dimitra Kotzamani
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  3. Kleopas Kleopa
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  4. Andreas Plaitakis
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Correspondence to Cleanthe Spanaki.

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Spanaki, C., Kotzamani, D., Kleopa, K. et al. Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons. Mol Neurobiol 53, 5140–5148 (2016). https://doi.org/10.1007/s12035-015-9429-2

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  • DOI: https://doi.org/10.1007/s12035-015-9429-2

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