Why should we have wolfram research?​

It is crucial that we gain a complete understanding of the complexities of Wolfram Syndrome by performing rigorous research, which will serve as the platform to discover and clinically test successful treatment options. Researchers believe that finding a treatment and cure for Wolfram Syndrome may open doors for treating diabetes and other diseases such as Parkinson’s and Alzheimer’s.

Wolframin and SERCA – Molecular Partners​

Abstract

Wolfram syndrome is an autosomal recessive disorder characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein that is involved in the regulation of the unfolded protein response (UPR), intracellular ion homeostasis, cyclic adenosine monophosphate production and regulation of insulin biosynthesis and secretion.

In this study, single cell Ca2+ imaging with fura-2 and direct measurements of free cytosolic ATP concentration ([ATP]CYT) with adenovirally expressed luciferase confirmed a reduced and delayed rise in cytosolic free Ca2+ concentration ([Ca2+]CYT), and additionally, diminished [ATP]CYT rises in response to elevated glucose concentrations in WFS1-depleted MIN6 cells. We also observed that sarco(endo)plasmic reticulum ATPase (SERCA) expression was elevated in several WFS1-depleted cell models and primary islets. We demonstrated a novel interaction between WFS1 and SERCA by co-immunoprecipitation in Cos7 cells and with endogenous proteins in human neuroblastoma cells. This interaction was reduced when cells were treated with the ER stress inducer dithiothreitol. Treatment of WFS1-depleted neuroblastoma cells with the proteasome inhibitor MG132 resulted in reduced accumulation of SERCA levels compared with wild-type cells. Together these results reveal a role for WFS1 in the negative regulation of SERCA and provide further insights into the function of WFS1 in calcium homeostasis.

Full article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291252/

Publication: ncbi.nlm.nih.gov | Publication Date: September 30, 2014

Authors: Zatyka, M., Da Silva Xavier, G., Bellomo, E. A., Leadbeater, W., Astuti, D., Smith, J., Michelangeli, F., Rutter, G. A., & Barrett, T. G.

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