Glycosphingolipid storage leads to the enhanced degradation of the B cell receptor in Sandhoff disease mice.

te Vruchte, D; Jeans, A; Platt, F; Sillence, D

Journal article

Glycosphingolipid storage leads to the enhanced degradation of the B cell receptor in Sandhoff disease mice.

Abstract:: Glycosphingolipid storage diseases are a group of inherited metabolic diseases in which glycosphingolipids accumulate due to their impaired lysosomal breakdown. Splenic B cells isolated from NPC1, Sandhoff, GM1-gangliosidosis and Fabry disease mouse models showed large (20- to 30-fold) increases in disease specific glycosphingolipids and up to a 4-fold increase in cholesterol. The magnitude of glycosphingolipid storage was in the order NPC1 > Sandhoff approximately GM1 gangliosidosis > Fabry. Except for Fabry disease, glycosphingolipid storage led to an increase in the lysosomal compartment and altered glycosphingolipid trafficking. In order to investigate the consequences of storage on B cell function, the levels of surface expression of B cell IgM receptor and its associated components were quantitated in Sandhoff B cells, since they are all raft-associated on activation. Both the B cell receptor, CD21 and CD19 had decreased cell surface expression. In contrast, CD40 and MHC II, surface receptors that do not associate with lipid rafts, were unchanged. Using a pulse chase biotinylation procedure, surface B cell receptors on a Sandhoff lymphoblast cell line were found to have a significantly decreased half-life. Increased co-localization of fluorescently conjugated cholera toxin and lysosomes was also observed in Sandhoff B cells. Glycosphingolipid storage leads to the enhanced formation of lysosomal lipid rafts, altered endocytic trafficking and increased degradation of the B cell receptor.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

te Vruchte, D., Jeans, A., Platt, F., & Sillence, D. (2010). Glycosphingolipid storage leads to the enhanced degradation of the B cell receptor in Sandhoff disease mice. Journal of Inherited Metabolic Disease, 33(3), 261–270.

MLA Style

te Vruchte, D., et al. “Glycosphingolipid Storage Leads to the Enhanced Degradation of the B Cell Receptor in Sandhoff Disease Mice.” Journal of Inherited Metabolic Disease, vol. 33, no. 3, 2010, pp. 261–70.

Chicago Style

Vruchte, D te, A Jeans, F Platt, and D Sillence. 2010. “Glycosphingolipid Storage Leads to the Enhanced Degradation of the B Cell Receptor in Sandhoff Disease Mice.” Journal of Inherited Metabolic Disease 33 (3): 261–70.
Share
Print