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The Journal of biological chemistry v.292 no.7, 2017년, pp.2557 - 2570   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Physiological Exploration of the Long Term Evolutionary Selection against Expression of N-Glycolylneuraminic Acid in the Brain

Naito-Matsui, Yuko (From the Departments of Medicine and Cellular and Molecular Medicine, ) ; Davies, Leela R. L. (From the Departments of Medicine and Cellular and Molecular Medicine, ) ; Takematsu, Hiromu (From the Departments of Medicine and Cellular and Molecular Medicine, ) ; Chou, Hsun-Hua (From the Departments of Medicine and Cellular and Molecular Medicine, ) ; Tangvoranuntakul, Pam (From the Departments of Medicine and Cellular and Molecular Medicine, ) ; Carlin, Aaron F. (From the Departments of Medicine and Cellular and Molecular Medicine, ) ; Verhagen, Andrea (From the Departments of Medicine and Cellular and Molecular Medicine, ) ; Heyser, Charles J. (Neuroscience Behavioral Testing Core, ) ; Yoo, Seung-Wan (the Departments of Neurology and ) ; Choudhury, Biswa (Glycobiology Research and Training Center, and ) ; Paton, James C. (the Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia ) ; Paton, Adrienne W. (the Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia ) ; Varki, Nissi M. (Department of Pathol ) ; Schnaar, Ronald L. ; Varki, Ajit ;
  • 초록  

    All vertebrate cell surfaces display a dense glycan layer often terminated with sialic acids, which have multiple functions due to their location and diverse modifications. The major sialic acids in most mammalian tissues are N -acetylneuraminic acid (Neu5Ac) and N -glycolylneuraminic acid (Neu5Gc), the latter being derived from Neu5Ac via addition of one oxygen atom at the sugar nucleotide level by CMP-Neu5Ac hydroxylase (Cmah). Contrasting with other organs that express various ratios of Neu5Ac and Neu5Gc depending on the variable expression of Cmah, Neu5Gc expression in the brain is extremely low in all vertebrates studied to date, suggesting that neural expression is detrimental to animals. However, physiological exploration of the reasons for this long term evolutionary selection has been lacking. To explore the consequences of forced expression of Neu5Gc in the brain, we have established brain-specific Cmah transgenic mice. Such Neu5Gc overexpression in the brain resulted in abnormal locomotor activity, impaired object recognition memory, and abnormal axon myelination. Brain-specific Cmah transgenic mice were also lethally sensitive to a Neu5Gc-preferring bacterial toxin, even though Neu5Gc was overexpressed only in the brain and other organs maintained endogenous Neu5Gc expression, as in wild-type mice. Therefore, the unusually strict evolutionary suppression of Neu5Gc expression in the vertebrate brain may be explained by evasion of negative effects on neural functions and by selection against pathogens.


  • 주제어

    bacterial toxin .   brain .   ganglioside .   glycobiology .   sialic acid .   N-glycolylneuraminic acid .   behavior .   myelin-associated glycoprotein.  

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