Subunit interactions of the Golgi-resident GlcNac-1-phosphotransferase complex
Prof. Dr. Thomas Braulke (2008 – 2017)
PD Dr. Stephan Storch (2008 – 2012)
Dr. Sandra Pohl (2012 – 2017)
University Medical Center Hamburg-Eppendorf, Institute of Osteology and Biomechanics (TB, SP) / Children’s Hospital (StSt)
Mucolipidoses II and II are inherited lysosomal storage disorders which are caused by defects in the Golgi-localized GlcNAc-1-phosphotransferase complex. This enzyme complex is composed of six subunits, α2β2γ2, playing a key role in the generation of mannose 6-phosphate recognition marker on lysosomal hydrolases which are essential for their efficient transport to lysosomes. The membrane-bound α- and β-subunits of the GlcNAc-1-phosphotransferase are catalytically active whereas the function of the soluble γ-subunit is unclear. The aim of this project is to investigate the interactions of the γ-subunit with α- and/or β-subunits and to define structural requirements for protein binding. The functional significance of these interactions will be analyzed in patient or knock-out cells lacking the γ-subunit. Furthermore, the vesicular transport of the three subunits from the ER to the Golgi-apparatus will be examined.