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      Mucin-Type O-Glycosylation in the Drosophila Nervous System

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          Abstract

          Mucin-type O-glycosylation, a predominant type of O-glycosylation, is an evolutionarily conserved posttranslational modification in animals. Mucin-type O-glycans are often found on mucins in the mucous membranes of the digestive tract. These glycan structures are also expressed in other cell types, such as blood cells and nephrocytes, and have crucial physiological functions. Altered expression of mucin-type O-glycans is known to be associated with several human disorders, including Tn syndrome and cancer; however, the physiological roles of mucin-type O-glycans in the mammalian brain remains largely unknown. The functions of mucin-type O-glycans have been studied in the fruit fly, Drosophila melanogaster. The basic structures of mucin-type O-glycans, including Tn antigen (GalNAcα1-Ser/Thr) and T antigen (Galβ1–3GalNAcα1-Ser/Thr), as well as the glycosyltransferases that synthesize them, are conserved between Drosophila and mammals. These mucin-type O-glycans are expressed in the Drosophila nervous system, including the central nervous system (CNS) and neuromuscular junctions (NMJs). In primary cultured neurons of Drosophila, mucin-type O-glycans show a characteristic localization pattern in axons. Phenotypic analyses using mutants of glycosyltransferase genes have revealed that mucin-type O-glycans are required for CNS development, NMJ morphogenesis, and synaptic functions of NMJs in Drosophila. In this review, we describe the roles of mucin-type O-glycans in the Drosophila nervous system. These findings will provide insight into the functions of mucin-type O-glycans in the mammalian brain.

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          Most cited references58

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          Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family.

          Glycosylation of proteins is an essential process in all eukaryotes and a great diversity in types of protein glycosylation exists in animals, plants and microorganisms. Mucin-type O-glycosylation, consisting of glycans attached via O-linked N-acetylgalactosamine (GalNAc) to serine and threonine residues, is one of the most abundant forms of protein glycosylation in animals. Although most protein glycosylation is controlled by one or two genes encoding the enzymes responsible for the initiation of glycosylation, i.e. the step where the first glycan is attached to the relevant amino acid residue in the protein, mucin-type O-glycosylation is controlled by a large family of up to 20 homologous genes encoding UDP-GalNAc:polypeptide GalNAc-transferases (GalNAc-Ts) (EC 2.4.1.41). Therefore, mucin-type O-glycosylation has the greatest potential for differential regulation in cells and tissues. The GalNAc-T family is the largest glycosyltransferase enzyme family covering a single known glycosidic linkage and it is highly conserved throughout animal evolution, although absent in bacteria, yeast and plants. Emerging studies have shown that the large number of genes (GALNTs) in the GalNAc-T family do not provide full functional redundancy and single GalNAc-T genes have been shown to be important in both animals and human. Here, we present an overview of the GalNAc-T gene family in animals and propose a classification of the genes into subfamilies, which appear to be conserved in evolution structurally as well as functionally.
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            Drosophila tools and assays for the study of human diseases

            ABSTRACT Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes.
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              Shaping cells and organs in Drosophila by opposing roles of fat body-secreted Collagen IV and perlecan.

              Basement membranes (BMs) are resilient polymer structures that surround organs in all animals. Tissues, however, undergo extensive morphological changes during development. It is not known whether the assembly of BM components plays an active morphogenetic role. To study in vivo the biogenesis and assembly of Collagen IV, the main constituent of BMs, we used a GFP-based RNAi method (iGFPi) designed to knock down any GFP-trapped protein in Drosophila. We found with this method that Collagen IV is synthesized by the fat body, secreted to the hemolymph (insect blood), and continuously incorporated into the BMs of the larva. We also show that incorporation of Collagen IV determines organ shape, first by mechanically constricting cells and second through recruitment of Perlecan, which counters constriction by Collagen IV. Our results uncover incorporation of Collagen IV and Perlecan into BMs as a major determinant of organ shape and animal form. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Neuroanat
                Front Neuroanat
                Front. Neuroanat
                Frontiers in Neuroanatomy
                Frontiers Media S.A.
                1662-5129
                18 October 2021
                2021
                : 15
                : 767126
                Affiliations
                [1] 1Glycan & Life Systems Integration Center (GaLSIC), Soka University , Hachioji, Japan
                [2] 2Department of Biosciences, Graduate School of Science and Engineering, Soka University , Hachioji, Japan
                Author notes

                Edited by: Sei Saitoh, Fujita Health University, Japan

                Reviewed by: Chihiro Hama, Kyoto Sangyo University, Japan; Yuji Hara, University of Shizuoka, Japan; Kazuhiko Kume, Nagoya City University, Japan

                *Correspondence: Shoko Nishihara shoko@ 123456soka.ac.jp
                Article
                10.3389/fnana.2021.767126
                8558370
                80711175-a1d2-454e-a9d6-1e322f78306f
                Copyright © 2021 Itoh and Nishihara.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 August 2021
                : 29 September 2021
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 58, Pages: 8, Words: 6137
                Funding
                Funded by: Japan Agency for Medical Research and Development, doi 10.13039/100009619;
                Categories
                Neuroscience
                Mini Review

                Neurosciences
                mucin-type o-glycans,mucin-type o-glycosylation,t antigen,drosophila,nervous system,neuromuscular junction

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