Biosynthesis, processing, and intracellular transport of GM2 activator protein in human epidermal keratinocytes. The lysosomal targeting of the GM2 activator is independent of a mannose-6-phosphate signal.
The processing, intracellular transport, and endocytosis of the GM2 activator protein (GM2AP), an essential cofactor of beta-hexosaminidase A for the degradation of ganglioside GM2, was investigated in human epidermal keratinocytes. The GM2AP precursor is synthesized as an 18-kDa peptide, which is singly glycosylated, resulting in 22-kDa high mannose and 24-27-kDa complex glycoforms. A small portion of the 22-kDa form bears phosphomannosyl residues. About 30% of the GM2AP precursor is secreted during 12 h after synthesis, consisting almost exclusively of complex glycoforms. In a post-Golgi compartment, the intracellular remainder is converted to a 20-kDa mature form within 24 h, bearing a heavily trimmed N-glycan on a 17-kDa backbone. Interestingly, even nonglycosylated GM2AP is delivered to the lysosome, as shown by tunicamycin treatment and subcellular fractionation. Also, its endocytosis is independent of carbohydrate-linked signals and is even more effective for nonglycosylated GM2AP. We conclude that a mannose-6-phosphate-independent pathway for the lysosomal delivery of GM2AP exists in cultured human keratinocytes.
Glombitza
G J
GJ
Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Strasse 1, D-53121 Bonn, Federal Republic of Germany.
Becker
E
E
Kaiser
H W
HW
Sandhoff
K
K
D001692:Biological Transport; D004817:Epidermis / Q000378:metabolism*; D049289:G(M2) Activator Protein; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D014176:Protein Biosynthesis
D049289:G(M2) Activator Protein