NR AXTO
AU Watt, T.N.; Taylor,D.R.; Hooper,N.M.
TI Endocytosis of the Cellular Isoform of the Prion Protein and Neuronal Zinc Uptake
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.178
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Whilst an exact physiological function remains elusive for the cellular isoform of the prion protein (PrPc), an involvement in metal homeostasis is an extensively studied concept. To date, this work has centered upon copper metabolism, evaluating roles in binding and uptake of the ion. However, closer examination of available literature has revealed a possible role for PrPc in neuronal zinc homeostasis. Zinc has been shown to be able to bind at the octapeptide repeat sequence and induce endocytosis of the protein. Furthermore, an increase in zinc-bound PrPc was determined in affinity purified material from prion-infected mice. As there was a significant decrease in total zinc measured for the whole brain homogenate, it would imply a redistribution of zinc ions occurs within the brain during disease progression.
Aim: To ascertain whether expression of PrPc influenced zinc uptake and metabolism in neuronal SH-SY5Y cells.
Results: Using the zinc binding fluorochrome Zinpyr-1, we have been able to demonstrate a significant increase in staining following zinc supplementation in cells which were stably expressing PrPc. This staining was shown to be zinc specific as cells supplemented either with; Cu, Fe, Mn or Ca showed no increase in fluorescence. The pattern of increased staining was consistent with an increase in zinc uptake in the cells expressing PrPc. Further studies to address the effect of mutation in PrPc and the role of the recently identified endocytic partner for PrPc , LRP1, on the uptake of the ion are being investigated.
Conclusions: Taken together these data demonstrate a role for PrPc in the cellular uptake of zinc ions potentially demonstrating a novel physiological function for the protein.
Funded by the Medical Research Council of Great Britain and The Wellcome Trust
AD W. Nicole, D. Taylor, N. Hooper, Institute of Molecular and Cellular Biology, UK
SP englisch
PO Schottland