Glycosphingolipids - Sweets for botulinum neurotoxin

Brian C. Yowler, Cara-Lynne Schengrund

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

A number of viruses, bacteria, and bacterial toxins can only act on cells that express the appropriate glycosphingolipids (GSLs) on the outer surface of their plasma membranes. An example of this dependency is provided by botulinum neurotoxin (BoNT) which is synthesized by Clostridium botulinum and inhibits neurotransmission at the neuromuscular junction by catalyzing hydrolysis of a SNARE protein, thereby inducing a flaccid paralysis. Haemagglutinin components of progenitor forms of BoNT mediate its adherence to glycosphingolipids (GSLs) on intestinal epithelial cells while the cellular activity of most isolated serotypes requires the presence of certain gangliosides, especially those of the Gg1b family. This review discusses available information about the identity and the roles of GSLs in the activity of BoNT. Observations that serotypes A-F of BoNT require gangliosides for optimum activity (serotype G apparently does not), permits the hypothesis that it should be possible to develop an antagonist of this interaction thereby inhibiting/reducing its effect.

Original languageEnglish (US)
Pages (from-to)287-293
Number of pages7
JournalGlycoconjugate Journal
Volume21
Issue number6
DOIs
StatePublished - Nov 10 2004

Fingerprint

Glycosphingolipids
Neurotoxins
Gangliosides
Clostridium botulinum
Bacterial Toxins
SNARE Proteins
Clostridium
Neuromuscular Junction
Hemagglutinins
Cell membranes
Viruses
Synaptic Transmission
Paralysis
Hydrolysis
Bacteria
Epithelial Cells
Cell Membrane
Serogroup

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{cf2a0048678444a4b970a0e1b517dace,
title = "Glycosphingolipids - Sweets for botulinum neurotoxin",
abstract = "A number of viruses, bacteria, and bacterial toxins can only act on cells that express the appropriate glycosphingolipids (GSLs) on the outer surface of their plasma membranes. An example of this dependency is provided by botulinum neurotoxin (BoNT) which is synthesized by Clostridium botulinum and inhibits neurotransmission at the neuromuscular junction by catalyzing hydrolysis of a SNARE protein, thereby inducing a flaccid paralysis. Haemagglutinin components of progenitor forms of BoNT mediate its adherence to glycosphingolipids (GSLs) on intestinal epithelial cells while the cellular activity of most isolated serotypes requires the presence of certain gangliosides, especially those of the Gg1b family. This review discusses available information about the identity and the roles of GSLs in the activity of BoNT. Observations that serotypes A-F of BoNT require gangliosides for optimum activity (serotype G apparently does not), permits the hypothesis that it should be possible to develop an antagonist of this interaction thereby inhibiting/reducing its effect.",
author = "Yowler, {Brian C.} and Cara-Lynne Schengrund",
year = "2004",
month = "11",
day = "10",
doi = "10.1023/B:GLYC.0000046271.64647.fd",
language = "English (US)",
volume = "21",
pages = "287--293",
journal = "Glycoconjugate Journal",
issn = "0282-0080",
publisher = "Springer Netherlands",
number = "6",

}

Glycosphingolipids - Sweets for botulinum neurotoxin. / Yowler, Brian C.; Schengrund, Cara-Lynne.

In: Glycoconjugate Journal, Vol. 21, No. 6, 10.11.2004, p. 287-293.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Glycosphingolipids - Sweets for botulinum neurotoxin

AU - Yowler, Brian C.

AU - Schengrund, Cara-Lynne

PY - 2004/11/10

Y1 - 2004/11/10

N2 - A number of viruses, bacteria, and bacterial toxins can only act on cells that express the appropriate glycosphingolipids (GSLs) on the outer surface of their plasma membranes. An example of this dependency is provided by botulinum neurotoxin (BoNT) which is synthesized by Clostridium botulinum and inhibits neurotransmission at the neuromuscular junction by catalyzing hydrolysis of a SNARE protein, thereby inducing a flaccid paralysis. Haemagglutinin components of progenitor forms of BoNT mediate its adherence to glycosphingolipids (GSLs) on intestinal epithelial cells while the cellular activity of most isolated serotypes requires the presence of certain gangliosides, especially those of the Gg1b family. This review discusses available information about the identity and the roles of GSLs in the activity of BoNT. Observations that serotypes A-F of BoNT require gangliosides for optimum activity (serotype G apparently does not), permits the hypothesis that it should be possible to develop an antagonist of this interaction thereby inhibiting/reducing its effect.

AB - A number of viruses, bacteria, and bacterial toxins can only act on cells that express the appropriate glycosphingolipids (GSLs) on the outer surface of their plasma membranes. An example of this dependency is provided by botulinum neurotoxin (BoNT) which is synthesized by Clostridium botulinum and inhibits neurotransmission at the neuromuscular junction by catalyzing hydrolysis of a SNARE protein, thereby inducing a flaccid paralysis. Haemagglutinin components of progenitor forms of BoNT mediate its adherence to glycosphingolipids (GSLs) on intestinal epithelial cells while the cellular activity of most isolated serotypes requires the presence of certain gangliosides, especially those of the Gg1b family. This review discusses available information about the identity and the roles of GSLs in the activity of BoNT. Observations that serotypes A-F of BoNT require gangliosides for optimum activity (serotype G apparently does not), permits the hypothesis that it should be possible to develop an antagonist of this interaction thereby inhibiting/reducing its effect.

UR - http://www.scopus.com/inward/record.url?scp=7244248860&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7244248860&partnerID=8YFLogxK

U2 - 10.1023/B:GLYC.0000046271.64647.fd

DO - 10.1023/B:GLYC.0000046271.64647.fd

M3 - Review article

C2 - 15514477

AN - SCOPUS:7244248860

VL - 21

SP - 287

EP - 293

JO - Glycoconjugate Journal

JF - Glycoconjugate Journal

SN - 0282-0080

IS - 6

ER -