Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of Drosophila Male Meiosis.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Drosophila*/metabolism ; Drosophila Proteins*/metabolism; Animals ; Male ; Active Transport, Cell Nucleus ; Cytoplasm/metabolism ; Meiosis ; Nuclear Pore Complex Proteins/metabolism ; Cyclin B/metabolism

The cyclin-dependent kinase 1 (Cdk1)-cyclin B (CycB) complex plays critical roles in cell-cycle regulation. Before Drosophila male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex of the nuclear pore complex. When this export is inhibited, Cdk1 is not activated, and meiosis does not initiate. We investigated the mechanism that controls the cellular localization and activation of Cdk1. Cdk1-CycB continuously shuttled into and out of the nucleus before meiosis. Overexpression of CycB, but not that of CycB with nuclear localization signal sequences, rescued reduced cytoplasmic CycB and inhibition of meiosis in Nup62 -silenced cells. Full-scale Cdk1 activation occurred in the nucleus shortly after its rapid nuclear entry. Cdk1-dependent centrosome separation did not occur in Nup62- silenced cells, whereas Cdk1 interacted with Cdk-activating kinase and Twine/Cdc25C in the nuclei of Nup62- silenced cells, suggesting the involvement of another suppression mechanism. Silencing of roughex rescued Cdk1 inhibition and initiated meiosis. Nuclear export of Cdk1 ensured its escape from inhibition by a cyclin-dependent kinase inhibitor. The complex re-entered the nucleus via importin β at the onset of meiosis. We propose a model regarding the dynamics and activation mechanism of Cdk1-CycB to initiate male meiosis.

Biogerontology. 2015 Aug;16(4):485-501. (PMID: 25801590)
EMBO J. 1990 Aug;9(8):2563-72. (PMID: 2142452)
EMBO J. 1998 Jul 15;17(14):4127-38. (PMID: 9670027)
Development. 2015 Oct 1;142(19):3394-402. (PMID: 26443637)
EMBO Rep. 2021 Apr 7;22(4):e50994. (PMID: 33565211)
Dev Cell. 2010 Apr 20;18(4):533-43. (PMID: 20412769)
Dev Cell. 2020 Aug 10;54(3):379-394.e6. (PMID: 32579968)
Mol Biol Cell. 2016 Jul 1;27(13):2051-63. (PMID: 27170181)
Cell. 1992 Jun 12;69(6):977-88. (PMID: 1606618)
Traffic. 2014 Jul;15(7):727-48. (PMID: 24766099)
EMBO Rep. 2007 May;8(5):490-6. (PMID: 17431409)
Development. 2007 Aug;134(15):2851-61. (PMID: 17611222)
Curr Biol. 2004 Jun 22;14(12):1117-23. (PMID: 15203007)
Mol Neurodegener. 2022 Dec 8;17(1):80. (PMID: 36482422)
Curr Biol. 1997 Jul 1;7(7):488-99. (PMID: 9210381)
Development. 2010 Apr;137(8):1297-304. (PMID: 20223764)
Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7938-43. (PMID: 10393926)
Curr Biol. 1999 Jul 1;9(13):680-9. (PMID: 10395539)
J Cell Biol. 2009 Apr 20;185(2):193-202. (PMID: 19364923)
Cell. 2012 Jun 22;149(7):1500-13. (PMID: 22726437)
J Cell Biol. 1999 Jan 25;144(2):213-24. (PMID: 9922449)
Nat Struct Biol. 1996 Aug;3(8):696-700. (PMID: 8756328)
J Cell Sci. 2019 Sep 23;132(18):. (PMID: 31434716)
Dev Cell. 2013 Apr 29;25(2):207-19. (PMID: 23583758)
Prog Cell Cycle Res. 2003;5:335-47. (PMID: 14593728)
Dev Growth Differ. 2021 May;63(4-5):231-248. (PMID: 34050930)
Nat Methods. 2011 May;8(5):405-7. (PMID: 21460824)
Curr Biol. 2014 Jun 2;24(11):1276-82. (PMID: 24835456)
Cells. 2020 Jan 22;9(2):. (PMID: 31979075)
Development. 2007 Aug;134(15):2863-9. (PMID: 17611220)
Mol Biol Cell. 2011 Nov;22(21):3971-85. (PMID: 21900495)
Development. 1992 Oct;116(2):405-16. (PMID: 1286615)
J Cell Sci. 1993 Dec;106 ( Pt 4):1035-44. (PMID: 8126091)
Bioessays. 2016 Jul;38(7):627-43. (PMID: 27231150)
FEBS Lett. 2019 Oct;593(20):2868-2888. (PMID: 31602636)
Cell Div. 2007 May 04;2:12. (PMID: 17480229)
Curr Biol. 1999 Dec 2;9(23):1392-402. (PMID: 10607563)
Mol Cell Biol. 1997 Feb;17(2):571-83. (PMID: 9001210)
Trends Cell Biol. 1991 Nov;1(5):117-21. (PMID: 14731542)
Nat Rev Mol Cell Biol. 2017 Feb;18(2):73-89. (PMID: 27999437)
Cell. 1994 Jul 1;77(7):1015-25. (PMID: 8020092)
EMBO J. 1999 Apr 15;18(8):2184-95. (PMID: 10205172)
Nat Rev Mol Cell Biol. 2022 May;23(5):307-328. (PMID: 35058649)
PLoS Genet. 2020 Apr 6;16(4):e1008735. (PMID: 32251417)
J Cell Biol. 2019 Nov 4;218(11):3597-3611. (PMID: 31537708)
Mol Cell Biol. 2005 Apr;25(8):3364-87. (PMID: 15798220)
Nature. 2001 Mar 8;410(6825):215-20. (PMID: 11242082)
Genetics. 2014 Jan;196(1):197-210. (PMID: 24214341)
Cell Rep. 2022 Dec 27;41(13):111870. (PMID: 36577372)
Curr Opin Cell Biol. 2013 Dec;25(6):697-703. (PMID: 23849679)
Development. 1998 Jan;125(1):125-34. (PMID: 9389670)
J Cell Sci. 1994 Dec;107 ( Pt 12):3521-34. (PMID: 7706403)
Nat Commun. 2017 Nov 22;8(1):1701. (PMID: 29167465)
Mol Cell Biol. 1998 Jan;18(1):546-57. (PMID: 9418901)
Mech Dev. 1995 Oct;53(2):247-60. (PMID: 8562426)
Reproduction. 2010 Jan;139(1):11-21. (PMID: 19755484)
Curr Biol. 2013 Jan 21;23(2):127-32. (PMID: 23290553)
Biol Open. 2016 Aug 15;5(8):1011-21. (PMID: 27402967)
Development. 2013 Aug;140(15):3079-93. (PMID: 23861057)
Cell Struct Funct. 2019 Oct 23;44(2):121-135. (PMID: 31484839)
Cell Cycle. 2005 Apr;4(4):572-7. (PMID: 15876871)

17K07500 Japan Science and Technology Agency

Keywords: Drosophila; cyclin B; cyclin-dependent kinase 1; cyclin-dependent kinase inhibitor; male meiosis

0 (Drosophila Proteins)
0 (Nup62 protein, Drosophila)
0 (Nuclear Pore Complex Proteins)
0 (CycB protein, Drosophila)
0 (Cyclin B)

Date Created: 20231124 Date Completed: 20231127 Latest Revision: 20240201

20240202

PMC10670764

10.3390/cells12222611

37998346