• ISSN 1674-8301
  • CN 32-1810/R
Volume 36 Issue 4
Jul.  2022
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Article Contents
Cong-Rong Li, Ruo-Lei Wang, Shi-Ya Xie, Yan-Ru Li, Lei-Lei Gao, Zhi-Xia Yang, Dong Zhang. Fidgetin knockdown and knockout influences female reproduction distinctly in mice[J]. The Journal of Biomedical Research, 2022, 36(4): 269-279. doi: 10.7555/JBR.36.20220086
Citation: Cong-Rong Li, Ruo-Lei Wang, Shi-Ya Xie, Yan-Ru Li, Lei-Lei Gao, Zhi-Xia Yang, Dong Zhang. Fidgetin knockdown and knockout influences female reproduction distinctly in mice[J]. The Journal of Biomedical Research, 2022, 36(4): 269-279. doi: 10.7555/JBR.36.20220086

Fidgetin knockdown and knockout influences female reproduction distinctly in mice

doi: 10.7555/JBR.36.20220086
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  • Corresponding author: Dong Zhang and Zhi-Xia Yang, State Key Lab of Reproductive Medicine, Nanjing Medical University, 101 Longmian Ave, Nanjing, Jiangsu 211166, China. Tel/Fax: +86-25-86869504, E-mails: dong.ray.zhang@njmu.edu.cn and yang_zhixia@njmu.edu.cn
  • Received: 2022-04-16
  • Revised: 2022-05-24
  • Accepted: 2022-05-27
  • Published: 2022-07-10
  • Issue Date: 2022-07-28
  • Microtubule-severing proteins (MTSPs), are a family of proteins which use adenosine triphosphate to sever microtubules. MTSPs have been shown to play an important role in multiple microtubule-involved cellular processes. One member of this family, fidgetin (FIGN), is also involved in male fertility; however, no studies have explored its roles in female fertility. In this study, we found mouse fidgetin is rich within oocyte zona pellucida (ZP) and is the only MTSP member to do so. Fidgetin also appears to interact with all three ZP proteins. These findings prompted us to propose that fidgetin might prevent polyspermy. Results from in vitro maturation oocytes analysis showed that fidgetin knockdown did cause polyspermy. We then deleted all three fidgetin isoforms with CRISPR/Cas9 technologies; however, female mice remained healthy and with normal fertility. Of all mouse MTSPs, only the mRNA level of fidgetin-like 1 (FIGNL1) significantly increased. Therefore, we assert that fidgetin-like 1 compensates fidgetin's roles in fidgetin knockout female mice.

     

  • CLC number: R321.1, Document code: A
    The authors reported no conflict of interests.
    △These authors contributed equally to this work.
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  • [1]
    Roll-Mecak A, Vale RD. Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin[J]. Nature, 2008, 451(7176): 363–367. doi: 10.1038/nature06482
    [2]
    Johjima A, Noi K, Nishikori S, et al. Microtubule severing by katanin p60 AAA+ ATPase requires the C-terminal acidic tails of both α- and β-tubulins and basic amino acid residues in the AAA+ ring pore[J]. J Biol Chem, 2015, 290(18): 11762–11770. doi: 10.1074/jbc.M114.614768
    [3]
    Sharp DJ, Ross JL. Microtubule-severing enzymes at the cutting edge[J]. J Cell Sci, 2012, 125(11): 2561–2569. doi: 10.1242/jcs.101139
    [4]
    Roll-Mecak A, McNally FJ. Microtubule-severing enzymes[J]. Curr Opin Cell Biol, 2010, 22(1): 96–103. doi: 10.1016/j.ceb.2009.11.001
    [5]
    Kahn OI, Baas PW. Microtubules and growth cones: motors drive the turn[J]. Trends Neurosci, 2016, 39(7): 433–440. doi: 10.1016/j.tins.2016.04.009
    [6]
    Nakamura M. Microtubule nucleating and severing enzymes for modifying microtubule array organization and cell morphogenesis in response to environmental cues[J]. New Phytol, 2015, 205(3): 1022–1027. doi: 10.1111/nph.12932
    [7]
    Errico A, Ballabio A, Rugarli EI. Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics[J]. Hum Mol Genet, 2002, 11(2): 153–163. doi: 10.1093/hmg/11.2.153
    [8]
    Smith LB, Milne L, Nelson N, et al. KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility[J]. PLoS Genet, 2012, 8(5): e1002697. doi: 10.1371/journal.pgen.1002697
    [9]
    Dunleavy JEM, Okuda H, O'Connor AE, et al. Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse[J]. PLoS Genet, 2017, 13(11): e1007078. doi: 10.1371/journal.pgen.1007078
    [10]
    Cox GA, Mahaffey CL, Nystuen A, et al. The mouse fidgetin gene defines a new role for AAA family proteins in mammalian development[J]. Nat Genet, 2000, 26(2): 198–202. doi: 10.1038/79923
    [11]
    Yang Y, Mahaffey CL, Bérubé N, et al. Functional characterization of fidgetin, an AAA-family protein mutated in fidget mice[J]. Exp Cell Res, 2005, 304(1): 50–58. doi: 10.1016/j.yexcr.2004.11.014
    [12]
    L'Hôte D, Vatin M, Auer J, et al. Fidgetin-like1 is a strong candidate for a dynamic impairment of male meiosis leading to reduced testis weight in mice[J]. PLoS One, 2011, 6(11): e27582. doi: 10.1371/journal.pone.0027582
    [13]
    Fassier C, Fréal A, Gasmi L, et al. Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics[J]. J Cell Biol, 2018, 217(5): 1719–1738. doi: 10.1083/jcb.201604108
    [14]
    Kumar R, Duhamel M, Coutant E, et al. Antagonism between BRCA2 and FIGL1 regulates homologous recombination[J]. Nucl Acids Res, 2019, 47(10): 5170–5180. doi: 10.1093/nar/gkz225
    [15]
    Yuan J, Chen J. FIGNL1-containing protein complex is required for efficient homologous recombination repair[J]. Proc Natl Acad Sci U S A, 2013, 110(26): 10640–10645. doi: 10.1073/pnas.1220662110
    [16]
    Havlicek S, Kohl Z, Mishra HK, et al. Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons[J]. Hum Mol Genet, 2014, 23(10): 2527–2541. doi: 10.1093/hmg/ddt644
    [17]
    Kuo Y, Howard J. Cutting, amplifying, and aligning microtubules with severing enzymes[J]. Trends Cell Biol, 2021, 31(1): 50–61. doi: 10.1016/j.tcb.2020.10.004
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