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Function and Expression of Neural Glycans

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 11976

Special Issue Editor


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Guest Editor
Integrated Glyco-Molecular Science Center, Gifu University, Gifu, Japan
Interests: glyco-biochemistry; N-glycosylation; HNK-1; sugar analog; Alzheimer's disease

Special Issue Information

Dear Colleagues,

We all know that over half of mammalian proteins are glycosylated. Glycans on proteins and lipids, having a wide variety of structures, play pivotal roles in various biological events. In the nervous system, structurally unique glycans (e.g., HNK-1 epitope, polysialic acid, and so on) are expressed, and a number of studies have revealed that neural glycans are critically involved in neural development, synaptic plasticity, and development and aggravation of various neural disorders. However, not all functions of these neural glycans have been clarified, and little is known about how expression of these neural glycans is regulated. In this Special Issue, we deal with various types of neural glycans which have physiological and pathological functions in the nervous system. I believe that the papers in this issue will provide readers with new insights into the mechanisms of how neural glycans function and are regulated.

Dr. Yasuhiko Kizuka
Guest Editor

Manuscript Submission Information

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Keywords

  • carbohydrate
  • glycan
  • glycosyltransferase
  • nervous system
  • posttranslational modification
  • glycosylation

Published Papers (4 papers)

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Research

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22 pages, 4826 KiB  
Article
Comparative Studies of Polysialic Acids Derived from Five Different Vertebrate Brains
by Yi Yang, Ryo Murai, Yuka Takahashi, Airi Mori, Masaya Hane, Ken Kitajima and Chihiro Sato
Int. J. Mol. Sci. 2020, 21(22), 8593; https://doi.org/10.3390/ijms21228593 - 14 Nov 2020
Cited by 5 | Viewed by 2020
Abstract
Polysialic acid (polySia/PSA) is a linear homopolymer of sialic acid (Sia) that primarily modifies the neural cell adhesion molecule (NCAM) in mammalian brains. PolySia-NCAM not only displays an anti-adhesive function due to the hydration effect, but also possesses a molecule-retaining function via a [...] Read more.
Polysialic acid (polySia/PSA) is a linear homopolymer of sialic acid (Sia) that primarily modifies the neural cell adhesion molecule (NCAM) in mammalian brains. PolySia-NCAM not only displays an anti-adhesive function due to the hydration effect, but also possesses a molecule-retaining function via a direct binding to neurologically active molecules. The quality and quantity of polySia determine the function of polySia-NCAM and are considered to be profoundly related to the maintenance of normal brain functions. In this study, to compare the structures of polySia-NCAM in brains of five different vertebrates (mammals, birds, reptiles, amphibians, and fish), we adopted newly developed combinational methods for the analyses. The results revealed that the structural features of polySia considerably varied among different species. Interestingly, mice, as a mammal, possess eminently distinct types of polySia, in both quality and quantity, compared with those possessed by other animals. Thus, the mouse polySia is of larger quantities, of longer and more diverse chain lengths, and of a larger molecular size with higher negative charge, compared with polySia of other species. These properties might enable more advanced brain function. Additionally, it is suggested that the polySia/Sia ratio, which likely reflects the complexity of brain function, can be used as a new promising index to evaluate the intelligence of different vertebrate brains. Full article
(This article belongs to the Special Issue Function and Expression of Neural Glycans)
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20 pages, 4747 KiB  
Article
Combinational Analyses with Multiple Methods Reveal the Existence of Several Forms of Polysialylated Neural Cell Adhesion Molecule in Mouse Developing Brains
by Airi Mori, Yi Yang, Yuka Takahashi, Masaya Hane, Ken Kitajima and Chihiro Sato
Int. J. Mol. Sci. 2020, 21(16), 5892; https://doi.org/10.3390/ijms21165892 - 16 Aug 2020
Cited by 5 | Viewed by 2638
Abstract
Polysialic acid (polySia/PSA) is an anionic glycan polymer of sialic acid, and it mostly modifies the neural cell adhesion molecule (NCAM) in mammalian brains. Quality and quantity of the polySia of the polySia–NCAM is spatio-temporally regulated in normal brain development and functions, and [...] Read more.
Polysialic acid (polySia/PSA) is an anionic glycan polymer of sialic acid, and it mostly modifies the neural cell adhesion molecule (NCAM) in mammalian brains. Quality and quantity of the polySia of the polySia–NCAM is spatio-temporally regulated in normal brain development and functions, and their impairments are reported to be related to diseases, such as psychiatric disorders and cancers. Therefore, precise understanding of the state of polySia–NCAM structure would lead to the diagnosis of diseases for which their suitable evaluation methods are necessary. In this study, to develop these evaluation methods, structures of polySia–NCAM from mouse brains at six different developmental stages were analyzed by several conventional and newly developed methods. Integrated results of these experiments clearly demonstrated the existence of different types of polySia–NCAMs in developing brains. In addition, combinational analyses were shown to be useful for precise understanding of the quantity and quality of polySia, which can provide criteria for the diagnosis of diseases. Full article
(This article belongs to the Special Issue Function and Expression of Neural Glycans)
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11 pages, 3189 KiB  
Article
Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions
by Jyoji Morise, Saki Yamamoto, Ryosuke Midorikawa, Kogo Takamiya, Motohiro Nonaka, Hiromu Takematsu and Shogo Oka
Int. J. Mol. Sci. 2020, 21(14), 5101; https://doi.org/10.3390/ijms21145101 - 19 Jul 2020
Cited by 1 | Viewed by 2547
Abstract
The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1–4), and its abundance in the synapse determines the strength of synaptic activity. The formation of oligomers in the endoplasmatic reticulum (ER) is crucial [...] Read more.
The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1–4), and its abundance in the synapse determines the strength of synaptic activity. The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits’ ER-exit and translocation to the cell membrane. Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear. In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions. In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner. Unlike wild-type (WT) GluA1, GluA2WT rescued surface GluA2N370Q expression. Additionally, the expression of GluA1N63Q reduced the cell surface expression level of GluA1WT. In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate. Full article
(This article belongs to the Special Issue Function and Expression of Neural Glycans)
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Review

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13 pages, 1311 KiB  
Review
The Function of Sialidase Revealed by Sialidase Activity Imaging Probe
by Akira Minami, Yuuki Kurebayashi, Tadanobu Takahashi, Tadamune Otsubo, Kiyoshi Ikeda and Takashi Suzuki
Int. J. Mol. Sci. 2021, 22(6), 3187; https://doi.org/10.3390/ijms22063187 - 20 Mar 2021
Cited by 6 | Viewed by 4312
Abstract
Sialidase cleaves sialic acid residues from glycans such as glycoproteins and glycolipids. In the brain, desorption of the sialic acid by sialidase is essential for synaptic plasticity, learning and memory and synaptic transmission. BTP3-Neu5Ac has been developed for sensitive imaging of sialidase enzyme [...] Read more.
Sialidase cleaves sialic acid residues from glycans such as glycoproteins and glycolipids. In the brain, desorption of the sialic acid by sialidase is essential for synaptic plasticity, learning and memory and synaptic transmission. BTP3-Neu5Ac has been developed for sensitive imaging of sialidase enzyme activity in mammalian tissues. Sialidase activity in the rat hippocampus detected with BTP3-Neu5Ac increases rapidly by neuronal depolarization. It is presumed that an increased sialidase activity in conjunction with neural excitation is involved in the formation of the neural circuit for memory. Since sialidase inhibits the exocytosis of the excitatory neurotransmitter glutamate, the increased sialidase activity by neural excitation might play a role in the negative feedback mechanism against the glutamate release. Mammalian tissues other than the brain have also been stained with BTP3-Neu5Ac. On the basis of information on the sialidase activity imaging in the pancreas, it was found that sialidase inhibitor can be used as an anti-diabetic drug that can avoid hypoglycemia, a serious side effect of insulin secretagogues. In this review, we discuss the role of sialidase in the brain as well as in the pancreas and skin, as revealed by using a sialidase activity imaging probe. We also present the detection of influenza virus with BTP3-Neu5Ac and modification of BTP3-Neu5Ac. Full article
(This article belongs to the Special Issue Function and Expression of Neural Glycans)
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