Compensatory expression of human -Acetylglucosaminyl-1-phosphotransferase subunits in mucolipidosis type III gamma

Sandra Pohl (1) , Stephan Tiede (1) , Monica Castrichini (1) , Michael Cantz (2) , Volkmar Gieselmann (3) , Thomas Braulke (1)

1 Department of Biochemistry
2 Universität Heidelberg [Heidelberg] = Heidelberg University
3 Universität Bonn = University of Bonn

The -Acetylglucosaminyl-1-phosphotransferase plays a key role in the generation of mannose 6-phosphate (M6P) recognition markers essential for efficient transport of lysosomal hydrolases to lysosomes. The phosphotransferase is composed of six subunits (α, β, γ). The α- and β-subunits are catalytically active and encoded by a single gene, , whereas the γ-subunit encoded by is proposed to recognize conformational structures common to lysosomal enzymes. Defects in causes mucolipidosis type III gamma, which is characterized by missorting and cellular loss of lysosomal enzymes leading to lysosomal accumulation of storage material. Using plasmon resonance spectrometry, we showed that recombinant γ-subunit failed to bind the lysosomal enzyme arylsulfatase A. Additionally, the overexpression of the γ-subunit in COS7 cells did not result in hypersecretion of newly synthesized lysosomal enzymes expected for competition for binding sites of the endogenous phosphotransferase complex.

Mots clés: Mucolipidosis type III; GNPTG; Mannose 6-phosphate; Sorting of lysosomal enzymes; GlcNAc-1-phosphotransferase

Sandra Pohl, Stephan Tiede, Monica Castrichini, Michael Cantz, Volkmar Gieselmann, et al.. Compensatory expression of human -Acetylglucosaminyl-1-phosphotransferase subunits in mucolipidosis type III gamma. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2009, 1792 (3), pp.221. ⟨10.1016/j.bbadis.2009.01.009⟩. ⟨hal-00501603⟩