Biosynthesis, Processing, and Intracellular Transport of GM2 Activator Protein in Human Epidermal Keratinocytes

The processing, intracellular transport, and endocytosis of the G M2 activator protein (G M2 AP), an essential cofactor of β-hexosaminidase A for the degradation of ganglioside G M2 , was investigated in human epidermal keratinocytes. The G M2 AP precursor is synthesized as an 18-kDa peptide, which...

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Veröffentlicht in:The Journal of biological chemistry 1997-02, Vol.272 (8), p.5199-5207
Hauptverfasser: Glombitza, Gereon J., Becker, Elisabeth, Kaiser, Hans Wilhelm, Sandhoff, Konrad
Format: Artikel
Sprache:eng
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Zusammenfassung:The processing, intracellular transport, and endocytosis of the G M2 activator protein (G M2 AP), an essential cofactor of β-hexosaminidase A for the degradation of ganglioside G M2 , was investigated in human epidermal keratinocytes. The G M2 AP 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 G M2 AP 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 G M2 AP 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 G M2 AP. We conclude that a mannose-6-phosphate-independent pathway for the lysosomal delivery of G M2 AP exists in cultured human keratinocytes.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.8.5199