Journal article
Phase partitioning of GM1 and its bodipy-labeled analog determine their different binding to cholera toxin
- Abstract:
- Driven by interactions between lipids and proteins, biological membranes display lateral heterogeneity that manifests itself in a mosaic of liquid-ordered (Lo) or raft, and liquid-disordered (Ld) or non-raft domains with a wide range of different properties and compositions. In giant plasma membrane vesicles and giant unilamellar vesicles, specific binding of Cholera Toxin (CTxB) to GM1 glycolipids is a commonly used strategy to label raft domains or Lo membrane environments. However, these studies often use acyl-chain labeled bodipy-GM1 (bdGM1), whose headgroup accessibility and membrane order or phase partitioning may differ from those of GM1, rendering the interpretation of CTxB binding data quite problematic. To unravel the molecular basis of CTxB binding to GM1 and bdGM1, we explored the partitioning and the headgroup presentation of these gangliosides in the Lo and Ld phases using atomistic molecular dynamics simulations complemented by CTxB binding experiments. The conformation of both GM1 and bdGM1 was shown to be largely similar in the Lo and Ld phases. However, bdGM1 showed reduction in receptor availability when reconstituted into synthetic bilayer mixtures, highlighting that membrane phase partitioning of the gangliosides plays a considerable role in CTxB binding. Our results suggest that the CTxB binding is predominately modulated by the partitioning of the receptor to an appropriate membrane phase. Further, given that the Lo and Ld partitioning of bdGM1 differs from those of GM1, usage of bdGM1 for studying GM1 behavior in cells can lead to invalid interpretation of experimental data.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.4MB, Terms of use)
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- Publisher copy:
- 10.3389/fphys.2017.00252
Authors
+ Wolfson Foundation
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- Funding agency for:
- Eggeling, C
- Sezgin, E
- Grant:
- 104924/14/Z/14
- 104924/14/Z/14
+ German Federal Ministry of Education and Research
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- Funding agency for:
- Grzybek, M
- Grant:
- DZD e.V
+ Alfred Kordelin Foundation
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- Funding agency for:
- Rissanen, S
- Grant:
- Advanced Grant CROWDEDPRO-LIPIDS
+ Tampere University of Technology
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- Funding agency for:
- Rissanen, S
- Grant:
- Advanced Grant CROWDEDPRO-LIPIDS
+ FEBS
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- Funding agency for:
- Rissanen, S
- Grant:
- Advanced Grant CROWDEDPRO-LIPIDS
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Physiology More from this journal
- Volume:
- 8
- Issue:
- 252
- Pages:
- 1-7
- Publication date:
- 2017-05-09
- Acceptance date:
- 2017-04-10
- DOI:
- ISSN:
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1664-042X
- Language:
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English
- Keywords:
- Pubs id:
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pubs:698131
- UUID:
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uuid:d7fa752c-c3c1-46cf-b217-9b1144a6b780
- Local pid:
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pubs:698131
- Source identifiers:
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698131
- Deposit date:
-
2017-06-02
Terms of use
- Copyright holder:
- © 2017 Rissanen, et al
- Copyright date:
- 2017
- Notes:
- 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) or licensor 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.
- Licence:
- CC Attribution (CC BY)
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