Glycodelin A, not glycodelin S, is apoptotically active. Relevance of sialic acid modification.
Glycodelin, previously known as PP14 (placental protein-14), is a kernel lipocalin secreted by the glandular epithelium of the endometrium upon progesterone stimulation and by the seminal vesicles. The isoform of the protein present in female reproductive tissue, glycodelin A (GdA), and the male counterpart, glycodelin S (GdS), have identical amino acid sequences, but strikingly different N-linked glycans. It is well documented in literature that GdA is an immunosuppressive protein, and we have shown that this activity is due to its ability to induce apoptosis in activated T cells. The precise role of GdS in seminal plasma is not known. In this study, we report that GdS is not apoptotically active. We observe that the apoptotic activity requires the presence of sialic acid residues on the complex glycans, as in the case of GdA; however, complex glycans of GdS are non-sialylated. We have expressed the wild-type protein in Pichia pastoris, which does not add sialic acid to the secreted proteins, and confirmed our observations that the protein is apoptotically inactive in the non-sialylated form. Our results indicate that differential glycosylation modulates the function of the different glycodelin isoforms.
Mukhopadhyay
Debaditya
D
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
SundarRaj
Swathi
S
Alok
Anshula
A
Karande
Anjali A
AA
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism; D019169:Jurkat Cells; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid; D011257:Pregnancy Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012661:Semen / Q000378:metabolism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D000071816:Glycodelin; D006023:Glycoproteins; D007166:Immunosuppressive Agents; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D019158:N-Acetylneuraminic Acid