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Membrane restructuring following in situ sialidase digestion of gangliosides: Complex model bilayers by synchrotron radiation reflectivity.

Biochim. Biophys. Acta. 2017 May;1859(5):845-851. Epub 2017 Jan 10
Valeria Rondelli 1 , Paola Brocca 1 , Giovanna Fragneto 2 , Jean Daillant 3 , Cristina Tringali 1 , Laura Cantu' 4 , Elena Del Favero 1
Valeria Rondelli 1 , Paola Brocca 1 , Giovanna Fragneto 2 , Jean Daillant 3 , Cristina Tringali 1 , Laura Cantu' 4 , Elena Del Favero 1
+ et al

[No authors listed]

Author information
  • 1 Dept. of Medical Biotechnologies and Traslational Medicine, University of Milano, LITA, Via F.lli Cervi, 93, 20090 Segrate, Italy.
  • 2 Institut Laue-Langevin, 71 avenue des Martyrs, BP 156, 38042 Grenoble Cedex 9, France.
  • 3 Synchrotron SOLEIL, L'Orme des Merisiers, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex, France.
  • 4 Dept. of Medical Biotechnologies and Traslational Medicine, University of Milano, LITA, Via F.lli Cervi, 93, 20090 Segrate, Italy. Electronic address: laura.cantu@unimi.it.

摘要


Synchrotron radiation reflectometry was used to access the transverse structure of model membranes under the action of the human sialidase NEU2, down to the Ångström length scale. Model membranes were designed to mimic the lipid composition of so-called Glycosphingolipids Enriched Microdomains (GEMs), which are membrane platforms specifically enriched in cholesterol and sphingolipids, and where also typical signalling molecules are hosted. Gangliosides, glycosphingolipids containing one or more sialic acid residues, are asymmetrically embedded in GEMs, in the outer membrane leaflet where gangliosides are claimed to interact directly with growth-factor receptors, modulating their activation and then the downstream intracellular signalling pathways. Thus, membrane dynamics and signalling could be strongly influenced by the activity of enzymes regulating the membrane ganglioside composition, including sialidases. Our results, concerning the structure of single membranes undergoing in-situ enzymatic digestion, show that the outcome of the sialidase action is not limited to the emergence of lower-sialylated ganglioside species. In fact, membrane reshaping occurs, involving a novel arrangement of the headgroups on its surface. Thus, sialidase activity reveals to be a potential tool to control dynamically the structural properties of the membrane external leaflet of living cells, influencing both the morphology of the close environment and the extent of interaction among active molecules belonging to signalling platforms.

KEYWORDS: Biomembrane, GEMs, Gangliosides, NEU2, Single model membrane, X-ray reflectometry