Attenuation of fibroblast growth factor signaling by poly-N- acetyllactosamine type glycans

Kazuhiro Sugihara; Toshiaki K. Shibata; Kayoko Takata; Takako Kimura; Naohiro Kanayama; Roy Williams; Shingo Hatakeyama; Tomoya O. Akama; Chu Wei Kuo; Kay Hooi Khoo; Michiko N. Fukuda

doi:10.1016/j.febslet.2013.07.056

Attenuation of fibroblast growth factor signaling by poly-N- acetyllactosamine type glycans

Kazuhiro Sugihara, Toshiaki K. Shibata, Kayoko Takata, Takako Kimura, Naohiro Kanayama, Roy Williams, Shingo Hatakeyama, Tomoya O. Akama, Chu Wei Kuo, Kay Hooi Khoo, Michiko N. Fukuda

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	3195-3201
Number of pages	7
Journal	FEBS Letters
Volume	587
Issue number	19
DOIs	https://doi.org/10.1016/j.febslet.2013.07.056
Publication status	Published - 01-10-2013
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2013.07.056

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@article{cca98e7e83f846a8b44b6f15fb65f707,

title = "Attenuation of fibroblast growth factor signaling by poly-N- acetyllactosamine type glycans",

abstract = "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.",

author = "Kazuhiro Sugihara and Shibata, {Toshiaki K.} and Kayoko Takata and Takako Kimura and Naohiro Kanayama and Roy Williams and Shingo Hatakeyama and Akama, {Tomoya O.} and Kuo, {Chu Wei} and Khoo, {Kay Hooi} and Fukuda, {Michiko N.}",

note = "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 . ",

year = "2013",

month = oct,

day = "1",

doi = "10.1016/j.febslet.2013.07.056",

language = "English",

volume = "587",

pages = "3195--3201",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

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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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DO - 10.1016/j.febslet.2013.07.056

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JO - FEBS Letters

JF - FEBS Letters

IS - 19

ER -

Attenuation of fibroblast growth factor signaling by poly-N- acetyllactosamine type glycans

Abstract

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