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Lysosulfatide Regulates the Motility of a Neural Precursor Cell Line Via Calcium-mediated Process Collapse

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Abstract

Lysosulfatide is a derivative of the glycosphingolipid sulfatide. It is a major component of high density lipoproteins and was detected in the human brain. Here, we show that lysosulfatide acts as an extracellular signal regulating the migration of a neural precursor cell line (B35 neuroblastoma cells) by rapidly promoting process retraction and cell rounding. These cells express the lysosulfatide receptor S1P3 according to RT-PCR, western blotting and immunocytochemistry, but S1P3 does not mediate the effect since preincubation with three different compounds known to inhibit S1P3 did not block lysosulfatide-induced cell rounding. The signal transduction after stimulation with 3 μM lysosulfatide involves a rapid increase of [Ca2+]i which causes process retraction. This mechanism may be relevant under conditions where neural cells encounter elevated lysosulfatide levels as for example under pathological conditions after breakdown of the blood brain barrier or possibly in the lysosomal sulfatide storage disorder metachromatic leukodystrophy.

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Abbreviations

ASA:

Arylsulfatase A

CNS:

Central nervous system

EDG:

Endothelial cell differentiation gene

HDL:

High density lipoprotein

Iono:

Ionomycin

Lyso:

Lysosulfatide

MLD:

Metachromatic leukodystrophy

RT:

Reverse transcription

S1P:

Sphingosine-1-phosphate

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Acknowledgement

We thank Norbert Rösel and Margit Zweyer for excellent technical assistance and Prof K. R. Lynch, University of Virginia (Charlottesville), for the generous gift of VPC25239. Supported by BMBF grant 01GN0502 to J.K. and V.G.

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Authors and Affiliations

  1. Institute of Physiology II, University of Bonn, Wilhelmstr. 31, 53111, Bonn, Germany

    M. Hans & D. Swandulla

  2. Institute of Physiological Chemistry, University of Bonn, Nussallee 11, 53115, Bonn, Germany

    A. Pusch, L. Dai, V. Gieselmann & J. Kappler

  3. Institute of Pharmacology and Toxicology, University of Bonn, Reuterstrasse 2b, 53113, Bonn, Germany

    K. Racké

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  1. M. Hans
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Correspondence to J. Kappler.

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Hans, M., Pusch, A., Dai, L. et al. Lysosulfatide Regulates the Motility of a Neural Precursor Cell Line Via Calcium-mediated Process Collapse. Neurochem Res 34, 508–517 (2009). https://doi.org/10.1007/s11064-008-9813-7

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  • DOI: https://doi.org/10.1007/s11064-008-9813-7

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