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Gangliosides: Modes of Action and Cell Fates II
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Gangliosides: Modes of Action and Cell Fates II

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 2021) | Viewed by 6676

Special Issue Editor

Prof. Dr. Koichi Furukawa

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai 487-8501, Japan
Interests: glycosphingolipids; neuronal cell; glioma cell; cancer; glycosylation; gangliosides; inflammation; neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gangliosides, sialic acid-containing glycosphingolipids, are mainly expressed on the cell membrane in vertebrates. The structure of the carbohydrate moieties varies depending on the development and differentiation states of tissues and cells. In particular, the polymorphic alteration of gangliosides along with the development and differentiation of nervous tissues has suggested their roles in the organogenesis of the nervous system. On the other hand, some gangliosides are considered to be cancer-associated antigens and have been used as tumor markers and targets for antibody therapy. Since cDNAs for ganglioside synthases were isolated, the genetic modification of ganglioside expression in cultured cells and experimental animals has enabled us to substantially elucidate the roles of gangliosides in cancers and the nervous system. The main findings can be summarized as follows: (i) Gangliosides play a pivotal role in the maintenance of the integrity of the nervous system and also in the repair of damaged nerves; (ii) Gangliosides are important for the architecture and function of membrane microdomains such as lipid rafts; and (iii) Gangliosides regulate cell signals in lipid rafts based on the interaction with ganglioside-recognizing molecules, influencing the cell fate. The formation of molecular clusters around gangliosides is now attracting the attention of many researchers in this field. We would like to focus on the modes of action of gangliosides and resulting cell fates to further understand the role of these molecules in the human body. This Special Issue calls for original research articles, reviews, and perspectives that address our current knowledge and progress in the research on gangliosides, focusing on their modes of action, and their influence on cell fate. In the 2nd version, articles regarding regulatory systems of ganglioside behaviors and basic analysis aiming application of ganglioside functions in clinical will be included.

Prof. Dr. Koichi Furukawa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • acidic glycosphingolipids 
  • microdomains and lipid rafts 
  • molecular complex formation 
  • regulation of signaling 
  • cell–cell interaction 
  • recognition and interaction with glycolipids 
  • proliferation and differentiation 
  • activation and inactivation

Published Papers (2 papers)

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Research

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20 pages, 3920 KiB  
Article
Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins
by Farhana Yesmin, Robiul H. Bhuiyan, Yuhsuke Ohmi, Satoko Yamamoto, Kei Kaneko, Yuki Ohkawa, Pu Zhang, Kazunori Hamamura, Nai-Kong V. Cheung, Norihiro Kotani, Koichi Honke, Tetsuya Okajima, Mariko Kambe, Orie Tajima, Keiko Furukawa and Koichi Furukawa
Int. J. Mol. Sci. 2022, 23(1), 423; https://doi.org/10.3390/ijms23010423 - 31 Dec 2021
Cited by 16 | Viewed by 3309
Abstract
Gangliosides have been considered to modulate cell signals in the microdomain of the cell membrane, lipid/rafts, or glycolipid-enriched microdomain/rafts (GEM/rafts). In particular, cancer-associated gangliosides were reported to enhance the malignant properties of cancer cells. In fact, GD2-positive (GD2+) cells showed increased proliferation, invasion, [...] Read more.
Gangliosides have been considered to modulate cell signals in the microdomain of the cell membrane, lipid/rafts, or glycolipid-enriched microdomain/rafts (GEM/rafts). In particular, cancer-associated gangliosides were reported to enhance the malignant properties of cancer cells. In fact, GD2-positive (GD2+) cells showed increased proliferation, invasion, and adhesion, compared with GD2-negative (GD2−) cells. However, the precise mechanisms by which gangliosides regulate cell signaling in GEM/rafts are not well understood. In order to analyze the roles of ganglioside GD2 in the malignant properties of melanoma cells, we searched for GD2-associating molecules on the cell membrane using the enzyme-mediated activation of radical sources combined with mass spectrometry, and integrin β1 was identified as a representative GD2-associating molecule. Then, we showed the physical association of GD2 and integrin β1 by immunoprecipitation/immunoblotting. Close localization was also shown by immuno-cytostaining and the proximity ligation assay. During cell adhesion, GD2+ cells showed multiple phospho-tyrosine bands, i.e., the epithelial growth factor receptor and focal adhesion kinase. The knockdown of integrin β1 revealed that the increased malignant phenotypes in GD2+ cells were clearly cancelled. Furthermore, the phosphor-tyrosine bands detected during the adhesion of GD2+ cells almost completely disappeared after the knockdown of integrin β1. Finally, immunoblotting to examine the intracellular distribution of integrins during cell adhesion revealed that large amounts of integrin β1 were localized in GEM/raft fractions in GD2+ cells before and just after cell adhesion, with the majority being localized in the non-raft fractions in GD2− cells. All these results suggest that GD2 and integrin β1 cooperate in GEM/rafts, leading to enhanced malignant phenotypes of melanomas. Full article
(This article belongs to the Special Issue Gangliosides: Modes of Action and Cell Fates II)
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Review

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17 pages, 1155 KiB  
Review
Roles of Gangliosides in Hypothalamic Control of Energy Balance: New Insights
by Kei-ichiro Inamori and Jin-ichi Inokuchi
Int. J. Mol. Sci. 2020, 21(15), 5349; https://doi.org/10.3390/ijms21155349 - 28 Jul 2020
Cited by 10 | Viewed by 2882
Abstract
Gangliosides are essential components of cell membranes and are involved in a variety of physiological processes, including cell growth, differentiation, and receptor-mediated signal transduction. They regulate functions of proteins in membrane microdomains, notably receptor tyrosine kinases such as insulin receptor (InsR) and epidermal [...] Read more.
Gangliosides are essential components of cell membranes and are involved in a variety of physiological processes, including cell growth, differentiation, and receptor-mediated signal transduction. They regulate functions of proteins in membrane microdomains, notably receptor tyrosine kinases such as insulin receptor (InsR) and epidermal growth factor receptor (EGFR), through lateral association. Studies during the past two decades using knockout (KO) or pharmacologically inhibited cells, or KO mouse models for glucosylceramide synthase (GCS; Ugcg), GM3 synthase (GM3S; St3gal5), and GD3 synthase (GD3S; St8sia1) have revealed essential roles of gangliosides in hypothalamic control of energy balance. The a-series gangliosides GM1 and GD1a interact with leptin receptor (LepR) and promote LepR signaling through activation of the JAK2/STAT3 pathway. Studies of GM3S KO cells have shown that the extracellular signal-regulated kinase (ERK) pathway, downstream of the LepR signaling pathway, is also modulated by gangliosides. Recent studies have revealed crosstalk between the LepR signaling pathway and other receptor signaling pathways (e.g., InsR and EGFR pathways). Gangliosides thus have the ability to modulate the effects of leptin by regulating functions of such receptors, and by direct interaction with LepR to control signaling. Full article
(This article belongs to the Special Issue Gangliosides: Modes of Action and Cell Fates II)
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