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Overexpression of mouse GlcNAc-1-phosphotransferase-gamma subunit in cells induced an I-cell-like phenotype of mucolipidosis
- Source :
- Gene. 347(1)
- Publication Year :
- 2003
-
Abstract
- In a screen of signal peptide-containing proteins from a mouse hypothetical protein library, we identified the mouse UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase-gamma chain (GlcNAc-1-phosphotransferase-gamma) (GenBank accession no. , HYP36 in this study). The mouse GlcNAc-1-phosphotransferase-gamma was localized in the Golgi complex in cells and was expressed ubiquitously in mouse tissues, as shown by fluorescence microscope analysis and a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, respectively. Domain analysis showed that the mouse GlcNAc-1-phosphotransferase-gamma had a conserved mannose-6-phosphate (M-6-P)-binding domain. Interestingly, we found that overexpression of the mouse GlcNAc-1-phosphotransferase-gamma in fibroblast cell line NIH-3T3 induced accumulation of macromolecules, formation of large cytoplasmic vacuoles and decrease of lysosomal enzymes in cells. This phenotype was reminiscent of inclusion cells (I-cells) that were reported in mucolipidosis diseases caused by abnormal sorting of lysosomal proteins. Transient ectopic expression of GlcNAc-1-phosphotransferase-gamma in endoplasmic reticulum (ER) induced lowered lysosomal enzyme activity in cells. These results suggested on one hand that GlcNAc-1-phosphotransferase-gamma is an essential subunit of the GlcNAc-1-phosphotransferase, and on the other hand, the molecule might not only recognize the substrates of GlcNAc-1-phosphotransferase, but also the lysosomal proteins with M-6-P residuals.
- Subjects :
- Protein subunit
Gene Expression
Golgi Apparatus
Transferases (Other Substituted Phosphate Groups)
Biology
medicine.disease_cause
N-Acetylglucosaminyltransferases
symbols.namesake
Mice
Mucolipidoses
Protein targeting
Genetics
medicine
Animals
Mannose 6-phosphate receptor
Mannosephosphates
Mucolipidosis
Endoplasmic reticulum
General Medicine
Golgi apparatus
medicine.disease
Molecular biology
Cell biology
Protein Structure, Tertiary
carbohydrates (lipids)
Cytoplasm
Vacuoles
symbols
NIH 3T3 Cells
Ectopic expression
Lysosomes
Subjects
Details
- ISSN :
- 03781119
- Volume :
- 347
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Gene
- Accession number :
- edsair.doi.dedup.....5700b1469d9010f1b7de5bfe8e2e2bf8