Translational research into hereditary spastic paraplegia (HSP)
Subproject 4
Project lead: Christian Hübner (Universität Jena)
We were able to show that upregulation and mislocalization of PI4K2alpha to autolysosomes occurs upon disruption of SPG11 or SPG15. PI4K2alpha phosphorylates phosphatidylinositol at position 4, leading to the formation of phosphatidylinositol 4-phosphate (PI4P), which is a precursor for other phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate, and an essential signaling molecule. The result of the mislocalization is a changed spectrum of local phosphoinositide levels, with important cellular consequences. We are currently studying whether our findings can be confirmed in cell lines derived from patients suffering from SPG11 and SPG15. If this will be the case, we will try various in vitro strategies to correct this defect and hopefully improve cellular functions. If succesful, we will then test these strategies in mouse models for SPG11.