title: Dynamin 2 is essential for mammalian spermatogenesis.
abstract: The dynamin family of proteins play important regulatory roles in membrane remodelling and endocytosis, especially within brain and neuronal tissues. In the context of reproduction, dynamin 1 (DNM1) and dynamin 2 (DNM2) have recently been shown to act as key mediators of sperm acrosome formation and function. However, little is known about the roles that these proteins play in the developing testicular germ cells. In this study, we employed a DNM2 germ cell-specific knockout model to investigate the role of DNM2 in spermatogenesis. We demonstrate that ablation of DNM2 in early spermatogenesis results in germ cell arrest during prophase I of meiosis, subsequent loss of all post-meiotic germ cells and concomitant sterility. These effects become exacerbated with age, and ultimately result in the demise of the spermatogonial stem cells and a Sertoli cell only phenotype. We also demonstrate that DNM2 activity may be temporally regulated by phosphorylation of DNM2 via the kinase CDK1 in spermatogonia, and dephosphorylation by phosphatase PPP3CA during meiotic and post-meiotic spermatogenesis.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.|PRC in Chemical Biology, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Kate A
authors.initials: KA
authors.lastname: Redgrove
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.|PRC in Chemical Biology, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Ilana R
authors.initials: IR
authors.lastname: Bernstein
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.|PRC in Chemical Biology, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Pye
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Bettina P
authors.initials: BP
authors.lastname: Mihalas
authors.affiliation: School of Biomedical Sciences &Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Jessie M
authors.initials: JM
authors.lastname: Sutherland
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.|PRC in Chemical Biology, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Nixon
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.|PRC in Chemical Biology, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: McCluskey
authors.affiliation: Cell Signalling Unit, Children's Medical Research Institute, University of Sydney, Sydney, NSW 2145, Australia.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.|PRC in Chemical Biology, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Holt
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.|PRC in Chemical Biology, University of Newcastle, Callaghan, NSW 2308, Australia.|School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand.
authors.forename: Eileen A
authors.initials: EA
authors.lastname: McLaughlin
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D002454:Cell Differentiation; D034285:Dynamin II / Q000378:metabolism*; D055786:Gene Knockout Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology / Q000502:physiology*
chemical_list: D016203:CDC2 Protein Kinase; D019703:Calcineurin; D034285:Dynamin II