Lipid Sorting by Ceramide Structure from Plasma Membrane to ER for the Cholera Toxin Receptor Ganglioside GM1

Chinnapen, Daniel J.‐F.; Hsieh, Wan-Ting; Welscher, Yvonne M. te; Saslowsky, David E.; Kaoutzani, Lydia; Brandsma, Eelke; D’Auria, Ludovic; Park, Hye-Jung; Wagner, Jessica; Drake, Kimberly R.; Kang, Minchul; Benjamin, Thomas L.; Ullman, M. David; Costello, Catherine E.; Kenworthy, Anne K.; Baumgart, Tobias; Massol, Ramiro; Lencer, Wayne I.

doi:10.1016/j.devcel.2012.08.002

Cited by 127 publications

(163 citation statements)

References 70 publications

(110 reference statements)

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“…Moreover, a retracing study of CT intoxicating retrograde pathways carried out using a subset of GM1 specified by saturated or unsaturated fluorescent-labeled ceramide chains showed that CT bound to saturated GM1, differently from the unsaturated complex forms, are directed towards late endosome compartments (that includes the MVB containing exosomes) rather than the classical Golgi/ER pathway [35]. Accordingly, it has been reported that GM1 gangliosides localize in the membrane of exosomes [36].…”

Section: Discussionmentioning

confidence: 99%

“…Based on our results an appealing speculation is that CTA associated with exo may derive from two distinct intracellular routes. One envisage that upon cell entry part of CT molecules may follow the long chain saturated GM1 pathway [35] presumably along with Cav-1, that leads to the CT holotoxin direct sorting to the late endosomal compartment/MVB before being secreted. The other, namely CTA1, is originated from the canonical ER retrograde pathway where, by the action of HSP90 and PDI, is translocated to the cytosol and taken up during exo formation by intraluminal vesicles.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cell Propagation of Cholera Toxin CTA ADP-Ribosylating Factor by Exosome Mediated Transfer

Zanetti¹,

Gallina²,

Fabbri³

et al. 2018

Preprint

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Abstract:Here we first report, how cholera toxin (CT) A subunit (CTA), the bacterial enzyme moiety responsible of cell signaling alteration, can take over the exosomal pathway, spread extracellularly and be transmitted in a cell population. A first evidence for long-term transmission of CT toxic effect via extracellular vesicles was obtained in CHO cells. To follow CT intracellular route towards exosome secretion we adopted a strategy apt to convert multivesicular body (MVB) derived exosomes in traceable fluorescent vectors. CT treated Me665 cells, a human melanoma cell line highly expressing caveolin-1 (Cav-1) and GM1, were used to purify and characterize fluorescent

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell Propagation of Cholera Toxin CTA ADP-Ribosylating Factor by Exosome Mediated Transfer

Zanetti¹,

Gallina²,

Fabbri³

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…For CT, this requires binding of its B subunit to the ganglioside receptor GM1, which acts as the vehicle for retrograde trafficking into the TGN and ER (1).…”

Section: Cholera Toxin (Ct)mentioning

confidence: 99%

Ganglioside GM1-mediated Transcytosis of Cholera Toxin Bypasses the Retrograde Pathway and Depends on the Structure of the Ceramide Domain

Saslowsky

Welscher

Chinnapen

et al. 2013

Journal of Biological Chemistry

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Background: Mechanisms for intracellular lipid sorting remain poorly understood. Results: Polarized epithelial cells sort ganglioside GM1, the receptor for cholera toxin, into distinct retrograde and transcytotic pathways, provided that GM1 contains ceramide domains with short or unsaturated fatty acid chains. Conclusion: Sphingolipid sorting depends on ceramide structure, implicating a mechanism for lipid sorting by lipid shape. Significance: The results identify a lipid-sorting pathway across epithelial barriers with clinical applications.

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“…However, this may relate to the presence of the ceramide moiety, which was absent from our a-GM1, rather than the GM1 glycan itself. Via this ceramide, GM1 and gangliosides generally would be expected to insert into the cellular plasma membrane under the experimental conditions used (43,73,74). This cellular GM1 incorporation might indirectly influence RRV recognition of its cellular receptors and/or reduce RRV cell entry by altering membrane lipid microdomains (lipid rafts), as GM1 partitions with lipid rafts.…”

Section: Discussionmentioning

confidence: 99%

Relative Roles of GM1 Ganglioside, N -Acylneuraminic Acids, and α2β1 Integrin in Mediating Rotavirus Infection

Fleming

Böhm

Dang

et al. 2014

J Virol

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N-acetyl-and N-glycolylneuraminic acids (Sia) and ␣2␤1 integrin are frequently used by rotaviruses as cellular receptors through recognition by virion spike protein VP4. The VP4 subunit VP8*, derived from Wa rotavirus, binds the internal N-acetylneuraminic acid on ganglioside GM1. Wa infection is increased by enhanced internal Sia access following terminal Sia removal from main glycan chains with sialidase. The GM1 ligand cholera toxin B (CTB) reduces Wa infectivity. Here, we found sialidase treatment increased cellular GM1 availability and the infectivity of several other human (including RV-3) and animal rotaviruses, typically rendering them susceptible to methyl ␣-D-N-acetylneuraminide treatment, but did not alter ␣2␤1 usage. CTB reduced the infectivity of these viruses. Aceramido-GM1 inhibited Wa and RV-3 infectivity in untreated and sialidasetreated cells, and GM1 supplementation increased their infectivity, demonstrating the importance of GM1 for infection. Wa recognition of ␣2␤1 and internal Sia were at least partially independent. Rotavirus usage of GM1 was mapped to VP4 using virus reassortants, and RV-3 VP8* bound aceramido-GM1 by saturation transfer difference nuclear magnetic resonance (STD NMR). Most rotaviruses recognizing terminal Sia did not use GM1, including RRV. RRV VP8* interacted minimally with aceramido-GM1 by STD NMR. Unusually, TFR-41 rotavirus infectivity depended upon terminal Sia and GM1. Competition of CTB, Sia, and/or aceramido-GM1 with cell binding by VP8* from representative rotaviruses showed that rotavirus Sia and GM1 preferences resulted from VP8*-cell binding. Our major finding is that infection by human rotaviruses of commonly occurring VP4 serotypes involves VP8* binding to cell surface GM1 glycan, typically including the internal N-acetylneuraminic acid. IMPORTANCERotaviruses, the major cause of severe infantile gastroenteritis, recognize cell surface receptors through virus spike protein VP4. Several animal rotaviruses are known to bind sialic acids at the termini of main carbohydrate chains. Conversely, only a single human rotavirus is known to bind sialic acid. Interestingly, VP4 of this rotavirus bound to sialic acid that forms a branch on the main carbohydrate chain of the GM1 ganglioside. Here, we use several techniques to demonstrate that other human rotaviruses exhibit similar GM1 usage properties. Furthermore, binding by VP4 to cell surface GM1, involving branched sialic acid recognition, is shown to facilitate infection. In contrast, most animal rotaviruses that bind terminal sialic acids did not utilize GM1 for VP4 cell binding or infection. These studies support a significant role for GM1 in mediating host cell invasion by human rotaviruses.

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Lipid Sorting by Ceramide Structure from Plasma Membrane to ER for the Cholera Toxin Receptor Ganglioside GM1

Cited by 127 publications

References 70 publications

Cell Propagation of Cholera Toxin CTA ADP-Ribosylating Factor by Exosome Mediated Transfer

Cell Propagation of Cholera Toxin CTA ADP-Ribosylating Factor by Exosome Mediated Transfer

Ganglioside GM1-mediated Transcytosis of Cholera Toxin Bypasses the Retrograde Pathway and Depends on the Structure of the Ceramide Domain

Relative Roles of GM1 Ganglioside, N -Acylneuraminic Acids, and α2β1 Integrin in Mediating Rotavirus Infection

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