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- Title
Posttranslational removal of α-dystroglycan N terminus by PC5/6 cleavage is important for uterine preparation for embryo implantation in women.
- Authors
Heng, Sophea; Paule, Sarah G.; Ying Li; Rombauts, Luk J.; Vollenhoven, Beverley; Salamonsen, Lois A.; Guiying Nie
- Abstract
Embryo implantation requires a healthy embryo and a receptive endometrium (inner lining of the uterus); endometrial receptivity acquisition involves considerable epithelial surface remodeling. Dystroglycan (DG), a large cell surface glycoprotein, consists of α- and β-subunits; β-DG anchors within the plasma membrane whereas α-DG attaches extracellularly to β-DG. The glycosylated central α-DG mediates adhesion, but it is obstructed by its large N terminus (α-DG-N); α-DG-N removal enables DG's adhesive function. We demonstrate here that full-length α-DG in the human endometrial epithelium is a barrier for embryo attachment and that removal of α-DG-N by proprotein convertase 5/6 (PC6; a protease critical for implantation) regulates receptivity. This was evidenced by: 1) α-DG contains a PC6-cleavage site near α-DG-N, and PC6 cleaves a peptide harboring such a site; 2) PC6 knockdown reduces α-DG-N removal from endometrial epithelial cell surface and blastocyst adhesion; 3) mutating the PC6-cleavage site prevents α-DG-N removal, causing cell surface retention of full-length α-DG and loss of adhesiveness; 4) α-DG-N is removed from endometrial tissue in vivo for receptivity and uterine fluid α-DG-N reflects tissue removal and receptivity. We thus identified α-DG-N removal as an important posttranslational control of endometrial receptivity and uterine fluid α-DG-N as a potential biomarker for receptivity in women.
- Subjects
ENDOMETRIUM; BIOMARKERS; GLYCOPROTEINS; CELL adhesion molecules; DYSTROGLYCAN; EMBRYO implantation
- Publication
FASEB Journal, 2015, Vol 29, Issue 9, p4011
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.14-269456