@article{e7e5cd5b232b42bba562b5fe411c4d24,
title = "Phosphoproteomics and bioinformatics analyses reveal key roles of gsk-3 and akap4 in mouse sperm capacitation",
abstract = "Protein phosphorylation can induce signal transduction to change sperm motility patterns during sperm capacitation. However, changes in the phosphorylation of sperm proteins in mice are still incompletely understood. Here, capacitation-related phosphorylation in mouse sperms were firstly investigated by label-free quantitative (LFQ) phosphoproteomics coupled with bioinformatics analysis using ingenuity pathway analysis (IPA) methods such as canonical pathway, upstream regulator, and network analysis. Among 1632 phosphopeptides identified at serine, threonine, and tyrosine residues, 1050 novel phosphosites, corresponding to 402 proteins, were reported. Gene heatmaps for IPA canonical pathways showed a novel role for GSK-3 in GP6 signaling pathways associated with capacitation for 60 min. At the same time, the reduction of the abundant isoform-specific GSK-3α expression was shown by western blot (WB) while the LFQ pY of this isoform slightly decreased and then increased. The combined results from WB and LFQ methods explain the less inhibitory phosphorylation of GSK-3α during capacitation and also support the predicted increases in its activity. In addition, pAKAP4 increased at the Y156 site but decreased at the Y811 site in a capacitated state, even though IPA network analysis and WB analysis for overall pAKAP revealed upregulated trends. The potential roles of GSK-3 and AKAP4 in fertility are discussed.",
keywords = "AKAP4, Bioinformatics, Capacitation, GSK-3, IPA, Mouse, Sperm",
author = "Nailis Syifa and Yang, {Jhih Tian} and Wu, {Chang Shiann} and Lin, {Miao Hsia} and Wu, {Wan Ling} and Lai, {Cheng Wei} and Ku, {Sheng Hsuan} and Liang, {Suh Yuen} and Hung, {Yu Chun} and Chou, {Chia Te} and Wang, {Chien Sheng} and Yasushi Ishihama and Liao, {Jiahn Haur} and Wu, {Shih Hsiung} and Wu, {Tzu Hua}",
note = "Funding Information: This study was supported by the Ministry of Science and Technology, Taiwan, under grant numbers NSC101-2313-B-038-003, NSC98-2313-B-038-002-MY3, and MOST104-2320-B-038-018 to T.-H.W. and NSC-101-2923-B-001-005-MY3, MOST-103-2113-M-001-029-MY3, MOST-103-2325-B-001-020, and MOST-104-2325-B-001-003 to S.-H.W. We acknowledge support from the Taiwan Protein Project (grant numbers: MOST105-0210-01-12-01, MOST106-0210-01-15-04, and MOST107-0210-01-19-02). Acknowledgments: N.S. is a recipient of a scholarship from the School of Pharmacy of Taipei Medical University financed by the Ministry of Science and Technology of Taiwan. N.S. is also supported by the Health Science Faculty University of Muhammadiyah Malang, Indonesia. We also acknowledge the GRC Mass Core Facility of the Genomics Research Center and the Academia Sinica Common Mass Spectrometry Facilities located at the Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan. Funding Information: Funding: This study was supported by the Ministry of Science and Technology, Taiwan, under grant numbers NSC101-2313-B-038-003, NSC98-2313-B-038-002-MY3, and MOST104-2320-B-038-018 to T.-H.W. and NSC-101-2923-B-001-005-MY3, MOST-103-2113-M-001-029-MY3, MOST-103-2325-B-001-020, and MOST-104-2325-B-001-003 to S.-H.W. We acknowledge support from the Taiwan Protein Project (grant numbers: MOST105-0210-01-12-01, MOST106-0210-01-15-04, and MOST107-0210-01-19-02). Funding Information: Acknowledgments: N.S. is a recipient of a scholarship from the School of Pharmacy of Taipei Medical University financed by the Ministry of Science and Technology of Taiwan. N.S. is also supported by the Health Science Faculty University of Muhammadiyah Malang, Indonesia. We also acknowledge the GRC Mass Core Facility of the Genomics Research Center and the Academia Sinica Common Mass Spectrometry Facilities located at the Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = oct,
day = "1",
doi = "10.3390/ijms21197283",
language = "English",
volume = "21",
pages = "1--17",
journal = "International journal of molecular sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "19",
}