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8.A.57 The Wofram Syndrom or Wolframin (Wolframin) Family

Wolfram syndrome is an autosomal recessive disorder in humans characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein with 890 aas and 10 putative TMSs 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.  A reduced and delayed rise in cytosolic free Ca2+ concentration and diminished [ATP] rises in response to elevated glucose concentrations in WFS1-depleted MIN6 cells has been demonstrated (Zatyka et al. 2015). Moreover, sarco(endo)plasmic reticulum ATPase (SERCA; TC# 3.A.3.2.7)) expression was elevated in several WFS1-depleted cell models and primary islets. Interaction between WFS1 and SERCA by co-immunoprecipitation was demonstrated. These results reveal a role for WFS1 in the negative regulation of SERCA and provide insight into the function of WFS1 in calcium homeostasis.

References associated with 8.A.57 family:

Zatyka, M., G. Da Silva Xavier, E.A. Bellomo, W. Leadbeater, D. Astuti, J. Smith, F. Michelangeli, G.A. Rutter, and T.G. Barrett. (2015). Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression. Hum Mol Genet 24: 814-827. 25274773