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 |
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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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.272.8.5199 |