TY - JOUR
T1 - Attenuation of fibroblast growth factor signaling by poly-N- acetyllactosamine type glycans
AU - Sugihara, Kazuhiro
AU - Shibata, Toshiaki K.
AU - Takata, Kayoko
AU - Kimura, Takako
AU - Kanayama, Naohiro
AU - Williams, Roy
AU - Hatakeyama, Shingo
AU - Akama, Tomoya O.
AU - Kuo, Chu Wei
AU - Khoo, Kay Hooi
AU - Fukuda, Michiko N.
N1 - Funding Information:
This study was supported by National Institutes of Health Grants CA33859 and EY014620 , Sanford-Burnham Medical Research Institute , La Jolla, California, USA, a Grant-in-Aid for Scientific Research B-23390388 and Challenging Exploratory Research 24659726 from the Japan Society for the Promotion of Science, Hamamatsu University School of Medicine , Shizuoka, Japan, and the Taiwan National Core Facility Program for Biotechnology , NSC Grant 100-2325-B-001-029 , Academia Sinica, Taipei, Taiwan. The authors thank Dr. Elise Lamar for editing the manuscript, and Xiayu Stacy Huang for assistance with statistical analysis. We thank Drs. David F. Smith and Jamie Heimburg-Molinaro for glycan array provided as core H by the Consortium for Functional Glycomics supported by NIH Grants GM62116 and GM098791 .
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Fibroblast growth factors (FGFs) and their receptors are expressed in a variety of mammalian tissues, playing a role in development and cell proliferation. While analyzing human sperm motility, we found that sperm treated with endo-β-galactosidase (EBG), which specifically hydrolyzes poly-N-acetyllactosamine type glycans (polyLacs), enhanced motility. Mass spectrometry analysis revealed that sperm-associated polyLacs are heavily fucosylated, consistent with Lewis Y antigen. Immunohistochemistry of epididymis using an anti-Lewis Y antibody before and after EBG treatment suggested that polyLacs carrying the Lewis Y epitope are synthesized in epididymal epithelia and secreted to seminal fluid. EBG-treated sperm elevated cAMP levels and calcium influx, indicating activation of fibroblast growth factor signaling. Seminal fluid polyLacs bound to FGFs in vitro, and impaired FGF-mediated signaling in HEK293T cells.
AB - Fibroblast growth factors (FGFs) and their receptors are expressed in a variety of mammalian tissues, playing a role in development and cell proliferation. While analyzing human sperm motility, we found that sperm treated with endo-β-galactosidase (EBG), which specifically hydrolyzes poly-N-acetyllactosamine type glycans (polyLacs), enhanced motility. Mass spectrometry analysis revealed that sperm-associated polyLacs are heavily fucosylated, consistent with Lewis Y antigen. Immunohistochemistry of epididymis using an anti-Lewis Y antibody before and after EBG treatment suggested that polyLacs carrying the Lewis Y epitope are synthesized in epididymal epithelia and secreted to seminal fluid. EBG-treated sperm elevated cAMP levels and calcium influx, indicating activation of fibroblast growth factor signaling. Seminal fluid polyLacs bound to FGFs in vitro, and impaired FGF-mediated signaling in HEK293T cells.
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U2 - 10.1016/j.febslet.2013.07.056
DO - 10.1016/j.febslet.2013.07.056
M3 - Article
C2 - 23968720
AN - SCOPUS:84884292087
VL - 587
SP - 3195
EP - 3201
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 19
ER -