Important results on the role of glycosphingolipids

Cellular glycosphingolipids determining intracellular sorting

Kirsten Sandvig (left) and first author Hilde Raa
Kirsten Sandvig (left) and first author Hilde Raa

In a new article from Kirsten Sandvig’s group - entitled "Glycosphingolipid Requirements for Endosome-to-Golgi Transport of Shiga Toxin" - whole cell lipidomics, confocal microscopy and biochemical methods for toxin studies have been used to investigate the role of glycosphingolipids in sorting from endosomes.
The article is a result of a collaboration between Oslo and Max Planck Institute, Dresden, and has recently been epublished in the well reputed journal "Traffic" (impact factor 6,53).

The authors sum up the findings in the articles as follows:

During recent years a number of protein complexes have been shown to be important for intracellular sorting and normal cell growth. However, changes in membrane lipids have been found to be associated with growth and metastasis of cancer cells, and it is clear that lipids have been ignored due to the difficulties involved in analysing these cellular constituents.

The planning of the current study as well as the cell biology and biochemical work were performed by Sandvig’s group at Department of Biochemistry at the Institute for Cancer Research at the Norwegian Radium Hospital, and the lipid analysis was carried out at Max Planck Institute in Dresden.

More than 250 lipid species were analyzed to investigate the role of these membrane constituents in intracellular transport. This analysis was performed using direct injection of whole cell lipid extracts with no chromatographic separation in advance. A number of studies during the last years have shown that phosporylated phosphatidylinositols play a role in binding of cytosolic proteins involved in transport in cells.

The current study shows that also the composition of glycosphingolipids influences the fate of internalized molecules as well as the cellular localization of sorting nexins, proteins involved in transport and regulation of cell growth. Furthermore, the data show that there is a more complex interaction between de novo synthesis and the level of different lipids than previously appreciated.

This article reveals that lipids clearly deserve more attention.


Links
:

Glycosphingolipid Requirements for Endosome-to-Golgi Transport of Shiga Toxin.
Raa H, Grimmer S, Schwudke D, Bergan J, Wälchli S, Skotland T, Shevchenko A, Sandvig K.
Traffic. 2009 May 6. [Epub ahead of print]

Kirsten Sandvig's group - Intracellular transport

Department of Biochemistry

Institute for Cancer Research