期刊
JOURNAL OF CELL SCIENCE
卷 116, 期 21, 页码 4319-4330出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.00720
关键词
galactosyltransferase; cytoplasmic domain; cell surface; phosphorylation
类别
资金
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD022590] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [R24CA088339] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR014668, P20RR011830] Funding Source: NIH RePORTER
- NCI NIH HHS [R24CA88339] Funding Source: Medline
- NCRR NIH HHS [1 S10 RR14668, P30 RR11830] Funding Source: Medline
- NICHD NIH HHS [HD22590] Funding Source: Medline
- NIDCR NIH HHS [DE07120] Funding Source: Medline
beta1,4-Galactosyltransferase I (GalT I) exists in two subcellular compartments where it performs two distinct functions. The majority of GalT I is localized in the Golgi complex where it participates in glycoprotein biosynthesis; however, a small portion of GalT I is expressed on the cell surface where it functions as a matrix receptor by binding terminal N-acetylglucosamine residues on extracellular glycoside ligands. The GalT I polypeptide occurs in two alternate forms that differ only in the length of their cytoplasmic domains. It is thought that the longer cytoplasmic domain is responsible for GalT I function as a cell surface receptor because of its ability to associate with the detergent-insoluble cytoskeleton. In this study, we demonstrate that the long GalT I cytoplasmic and transmembrane domains are capable of targeting a reporter protein to the plasma membrane, whereas the short cytoplasmic and transmembrane domains do not have this property. The surface-localized GalT I reporter protein partitions with the detergent-insoluble pool, a portion of which co-fractionates with caveolin-containing lipid rafts. Site-directed mutagenesis of the cytoplasmic domain identified a requirement for serine and threonine residues for cell surface expression and function. Replacing either the serine or threonine with aspartic acid reduces surface expression and function, whereas substitution with neutral alanine has no effect on surface expression or function. These results suggest that phosphorylation negatively regulates GalT I function as a surface receptor. Consistent with this, phasphorylation of the endogenous, full-length GalT I inhibits its stable expression on the cell surface. Thus, the 13 amino acid extension unique to the long GalT I isoform is required for GalT I expression on the cell surface, the function of which is regulated by phosphorylation.
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