The multi-tasked life of GM1 ganglioside, a true factotum of nature

Ledeen, Robert W.; Wu, Gusheng

doi:10.1016/j.tibs.2015.04.005

Cited by 193 publications

(198 citation statements)

References 141 publications

(184 reference statements)

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“…Finally, we note that many toxins and viruses utilize a multivalent glycolipid binding strategy to gain access to host cells (23,24). Further, clustering of glycolipids has been hypothesized to play a role in many cellular functions (25)(26)(27)(28). Our results validate the underlying assumption in these biological scenarios that clustering of glycolipids enables raft partitioning and stabilization.…”

supporting

confidence: 75%

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Raghunathan

Wong

Chinnapen

et al. 2017

Biophysical Journal

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Current models of lipid rafts propose that lipid domains exist as nanoscale compositional fluctuations and these fluctuations can potentially be stabilized into larger domains, consequently better compartmentalizing cellular functions. However, the mechanisms governing stabilized raft assembly and function remain unclear. Here, we test the role of glycolipid crosslinking as a raft targeting and ordering mechanism using the well-studied raft marker cholera toxin B pentamer (CTxB) that binds up to five GM1 glycosphingolipids to enter host cells. We show that when applied to cell-derived giant plasma membrane vesicles, a variant of CTxB containing only a single functional GM1 binding site exhibits significantly reduced partitioning to the ordered phase compared to wild-type CTxB with five binding sites. Moreover, monovalent CTxB does not stabilize membrane domains, unlike wild-type CTxB. These results support the long-held hypothesis that CTxB stabilizes raft domains via a lipid crosslinking mechanism and establish a role for crosslinking in the partitioning of CTxB to ordered domains.

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supporting

confidence: 75%

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Raghunathan

Wong

Chinnapen

et al. 2017

Biophysical Journal

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“…13,14 Monosialogangliosides GM1 play an important role in regulating Ca 2+ in the nucleus and maintaining neuronal homeostasis, which can affect neural function by modulating cell signaling, such as ERK1/2 phosphorylation and Na + /Ca 2+ exchanger. [15][16][17] Many studies have shown that GM1 gangliosides can play neuroprotective and neurorestorative roles in neuronal injury, as well as induce neuritogenesis and promote cell differentiation.…”

mentioning

confidence: 99%

Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system

Zou

Wang

Lei

et al. 2017

IJN

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For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood–brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.

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“…Glycosylation is by far the most complex form of protein [1,2] and lipid modification [3,4] in all domains of life. The tremendous diversity of glycoconjugate structures resulting from intricate biosynthetic pathways is a major factor hampering the assignment of functions to glycans chains.…”

Section: Glycosylation Disordersmentioning

confidence: 99%

Congenital disorders of glycosylation: a concise chart of glycocalyx dysfunction

Hennet

Cabalzar

2015

Trends in Biochemical Sciences

112

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Glycosylation is a ubiquitous modification of lipids and proteins. Despite the essential contribution of glycoconjugates to the viability of all living organisms, diseases of glycosylation in humans have only been identified over the past few decades. The recent development of next-generation DNA sequencing techniques has accelerated the pace of discovery of novel glycosylation defects. The description of multiple mutations across glycosylation pathways not only revealed tremendous diversity in functional impairments, but also pointed to phenotypic similarities, emphasizing the interconnected flow of substrates underlying glycan assembly. The current list of 100 known glycosylation disorders provides an overview of the significance of glycosylation in human development and physiology. Congenital disorders of glycosylation -a consice chart of glycocalyx dysfunctionThierry Hennet, Jürg Cabalzar Institute of Physiology, University of Zurich, CH-8057 Zurich, Switzerland AbstractGlycosylation is a ubiquitous modification of lipids and proteins. Despite the essential contribution of glycoconjugates to the viability of all living organisms, diseases of glycosylation in humans have only been identified over the past few decades. The recent development of next-generation DNA sequencing techniques has accelerated the pace of discovery of novel glycosylation defects. The description of multiple mutations across glycosylation pathways has revealed a tremendous diversity of functional impairments bus also pointed to phenotypic similarities emphasizing the interconnected flow of substrates underlying glycan assembly. The current list of 100 known glycosylation disorders provides an overview on the significance of glycosylation in human development and physiology. Highlights Congenital disorders underline the role of glycosylation in human development.  Next-gen sequencing techniques expanded the discovery of glycosylation gene defects.  The clinical variability of glycosylation disorders implies they are underdiagnosed. Glycosylation disordersGlycosylation is by far the most complex form of protein [1,2] and lipid modification [3,4] in all domains of life. The tremendous diversity of glycoconjugate structures resulting from intricate biosynthetic pathways is a major factor hampering the assignment of functions to glycans chains. Much has been learnt from the study of disrupted glycosylation genes in model organisms, thereby establishing numerous essential contributions of glycans in regulating cell and organ functions [5]. The study of human diseases of glycosylation brings additional insights by providing a more differentiated view on glycan functions. Indeed, most human mutations are hypomorphic, thus causing partial loss of glycosylation reactions that lead to variable clinical manifestations.Diseases of glycosylation are also referred to as congenital disorders of glycosylation (CDG). Given the heterogeneity of glycans, the clinical scope of CDG is considerable, ranging from nearly normal phenotypes to sever...

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The multi-tasked life of GM1 ganglioside, a true factotum of nature

Cited by 193 publications

References 141 publications

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system

Congenital disorders of glycosylation: a concise chart of glycocalyx dysfunction

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The multi-tasked life of GM1 ganglioside, a true factotum of nature

Cited by 193 publications

References 141 publications

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Penetration of blood&ndash;brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system

Congenital disorders of glycosylation: a concise chart of glycocalyx dysfunction

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Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system