Molecular analysis of the GlcNac-1-phosphotransferase.

TY - JOUR

T1 - Molecular analysis of the GlcNac-1-phosphotransferase.

AU - Braulke, Thomas

AU - Pohl, Sandra

AU - Storch, Stephan

PY - 2008

Y1 - 2008

N2 - Modification of the carbohydrate chains of soluble lysosomal enzymes with mannose 6-phosphate residues is a prerequisite for their mannose 6-phosphate receptor-dependent transport to lysosomes. GlcNac-1-phosphotransferase localized in the Golgi apparatus represents a hexameric alpha(2)beta(2)gamma(2) subunit complex and plays a key role in the formation of the mannose 6-phosphate recognition marker. Defects in the GlcNac-1-phosphotransferase complex cause two diseases, mucolipidosis type II and III, which are characterized by missorting and cellular loss of lysosomal enzymes, and lysosomal accumulation of storage material. The recent identification of two genes, GNPTAB and GNPTG, encoding the three subunits of GlcNac-1-phosphotransferase leads to an improvement of both pre- and postnatal diagnosis of affected individuals, and permits the analysis of structural requirements for efficient formation of mannose 6-phosphate residues on lysosomal enzymes. The alpha/beta subunits precursor matures by proteolytic cleavage and contains the catalytic activity as well as the capability to recognize lysosomal enzymes. The role of the gamma-subunits for activity, stability and oligomerization of the GlcNac-1-phosphotransferase subunits is still unclear.

AB - Modification of the carbohydrate chains of soluble lysosomal enzymes with mannose 6-phosphate residues is a prerequisite for their mannose 6-phosphate receptor-dependent transport to lysosomes. GlcNac-1-phosphotransferase localized in the Golgi apparatus represents a hexameric alpha(2)beta(2)gamma(2) subunit complex and plays a key role in the formation of the mannose 6-phosphate recognition marker. Defects in the GlcNac-1-phosphotransferase complex cause two diseases, mucolipidosis type II and III, which are characterized by missorting and cellular loss of lysosomal enzymes, and lysosomal accumulation of storage material. The recent identification of two genes, GNPTAB and GNPTG, encoding the three subunits of GlcNac-1-phosphotransferase leads to an improvement of both pre- and postnatal diagnosis of affected individuals, and permits the analysis of structural requirements for efficient formation of mannose 6-phosphate residues on lysosomal enzymes. The alpha/beta subunits precursor matures by proteolytic cleavage and contains the catalytic activity as well as the capability to recognize lysosomal enzymes. The role of the gamma-subunits for activity, stability and oligomerization of the GlcNac-1-phosphotransferase subunits is still unclear.

M3 - SCORING: Zeitschriftenaufsatz

JO - J INHERIT METAB DIS

JF - J INHERIT METAB DIS

SN - 0141-8955

ER -