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ROLE OF GSK3a IN SPERM FUNCTION AND MALE FERTILITY

Bhattacharjee, Rahul
http://orcid.org/0000-0001-8607-5756
http://rave.ohiolink.edu/etdc/view?acc_num=kent1532949151866613

Abstract Details

2018, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Glycogen synthase kinase 3 (GSK3) is a highly conserved protein-serine kinase regulating key cellular functions. In mammals GSK3 is expressed as two isoforms, GSK3a and GSK3ß, encoded by distinct genes. The catalytic domains of the two isoforms are 98% identical. In most tissues the two isoforms are functionally interchangeable, except in the developing embryo where GSK3ß is essential. One functional allele of either of the two isoforms is sufficient to maintain normal tissue functions. That is, 25% of the total GSK3 catalytic activity appears to be sufficient to maintain normalcy in cells and tissues. We have previously shown that both GSK3 isoforms are present in bovine, primate, and mouse sperm and suggested that they may play a role in epididymal initiation and regulation of sperm motility. Using genetic approaches, here we have tested requirement for each of the two GSK3 isoforms in testis and sperm. Both GSK3a and GSK3ß are expressed at high levels in testis coincident with the onset of spermatogenesis. Mice harboring a conditional knock out of GSK3ß in developing germ cells in testis are normal and fertile. By contrast, conditional knock out of GSK3a in developing testicular germ cells results in male infertility. Mice lacking one allele each of GSK3a and GSK3ß, i.e. heterozygous for both isoforms, are fertile. Despite overlapping expression and localization of the two isoforms in testis, GSK3ß does not substitute for loss of GSK3a. GSK3a is essential and irreplaceable in testis and sperm. Loss of GSK3a impairs sperm hexokinase activity resulting in low ATP levels. Low ATP and net adenine nucleotide levels in caudal sperm lacking GSK3a resemble immature caput epididymal sperm. Changes in the association of the protein phosphatase PP1¿2 with known protein interactors, which occurs during sperm maturation in the epididymis, is impaired in sperm lacking GSK3a. Localization of GSK3a is predominant in the principal piece suggesting this protein kinase binds to proteins in the sperm tail. We suggest that function of GSK3a is likely due to its isoform specific binding to sperm proteins. Testis and sperm are unique in their specific requirement of GSK3a for normal function and male fertility.
Srinivasan Vijayaraghavan, PhD (Committee Chair)
Douglas Kline, PhD (Committee Member)
Gary Koski, PhD (Committee Member)
Hamza Balci, PhD (Committee Member)
Songping Huang, PhD (Committee Member)
139 p.
Biochemistry; Biology; Cellular Biology; Molecular Biology
Kinase, GSK3,Spermatogenesis, Sperm, Phosphatase, PP1,Sperm motility, Reproduction, ATP, Hexokinase

Recommended Citations

Citations

  • Bhattacharjee, R. (2018). ROLE OF GSK3a IN SPERM FUNCTION AND MALE FERTILITY [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1532949151866613

    APA Style (7th edition)

  • Bhattacharjee, Rahul. ROLE OF GSK3a IN SPERM FUNCTION AND MALE FERTILITY . 2018. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1532949151866613.

    MLA Style (8th edition)

  • Bhattacharjee, Rahul. "ROLE OF GSK3a IN SPERM FUNCTION AND MALE FERTILITY ." Doctoral dissertation, Kent State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1532949151866613

    Chicago Manual of Style (17th edition)

kent1532949151866613
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This open access ETD is published by Kent State University and OhioLINK.