Structured clustering of the glycosphingolipid GM1 is required for membrane curvature induced by cholera toxin.

Abstract:

:AB5 bacterial toxins and polyomaviruses induce membrane curvature as a mechanism to facilitate their entry into host cells. How membrane bending is accomplished is not yet fully understood but has been linked to the simultaneous binding of the pentameric B subunit to multiple copies of glycosphingolipid receptors. Here, we probe the toxin membrane binding and internalization mechanisms by using a combination of superresolution and polarized localization microscopy. We show that cholera toxin subunit B (CTxB) can induce membrane curvature only when bound to multiple copies of its glycosphingolipid receptor, GM1, and the ceramide structure of GM1 is likely not a determinant of this activity as assessed in model membranes. A mutant CTxB capable of binding only a single GM1 fails to generate curvature either in model membranes or in cells, and clustering the mutant CTxB-single-GM1 complexes by antibody cross-linking does not rescue the membrane curvature phenotype. We conclude that both the multiplicity and specific geometry of GM1 binding sites are necessary for the induction of membrane curvature. We expect this to be a general rule of membrane behavior for all AB5 toxins and polyomaviruses that bind glycosphingolipids to invade host cells.

authors

Kabbani AM,Raghunathan K,Lencer WI,Kenworthy AK,Kelly CV

doi

10.1073/pnas.2001119117

subject

Has Abstract

pub_date

2020-06-30 00:00:00

pages

14978-14986

issue

26

eissn

0027-8424

issn

1091-6490

pii

2001119117

journal_volume

117

pub_type

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