• PMID: 24554764
• Gene Name: KDM3A
• Condition: Required for cytoskeletal rearrangements during spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Required for cytoskeletal rearrangements during spermatogenesis

Kdm3a lysine demethylase is an Hsp90 client required for cytoskeletal rearrangements during spermatogenesis

Kasioulis I, Syred HM, Tate P, Finch A, Shaw J, Seawright A, Fuszard M, Botting CH, Shirran S, Adams IR, Jackson IJ, van Heyningen V, Yeyati PL.

The lysine demethylase Kdm3a (Jhdm2a, Jmjd1a) is required for male fertility, sex determination, and metabolic homeostasis through its nuclear role in chromatin remodeling. Many histone-modifying enzymes have additional nonhistone substrates, as well as nonenzymatic functions, contributing to the full spectrum of events underlying their biological roles. We present two Kdm3a mouse models that exhibit cytoplasmic defects that may account in part for the globozoospermia phenotype reported previously. Electron microscopy revealed abnormal acrosome and manchette and the absence of implantation fossa at the caudal end of the nucleus in mice without Kdm3a demethylase activity, which affected cytoplasmic structures required to elongate the sperm head. We describe an enzymatically active new Kdm3a isoform and show that subcellular distribution, protein levels, and lysine demethylation activity of Kdm3a depended on Hsp90. We show that Kdm3a localizes to cytoplasmic structures of maturing spermatids affected in Kdm3a mutant mice, which in turn display altered fractionation of β-actin and γ-tubulin. Kdm3a is therefore a multifunctional Hsp90 client protein that participates directly in the regulation of cytoskeletal components. FAU - Kasioulis, Ioannis AU - Kasioulis I AD - MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1HH, United Kingdom Biomedical Sciences Research Complex Mass Spectrometry and Proteomics Facility, University of St. Andrews, St. Andrews, Fife KY16 9ST, United Kingdom. FAU - Syred, Heather M AU - Syred HM FAU - Tate, Peri AU - Tate P FAU - Finch, Andrew AU - Finch A FAU - Shaw, Joseph AU - Shaw J FAU - Seawright, Anne AU - Seawright A FAU - Fuszard, Matt AU - Fuszard M FAU - Botting, Catherine H AU - Botting CH FAU - Shirran, Sally AU - Shirran S FAU - Adams, Ian R AU - Adams IR FAU - Jackson, Ian J AU - Jackson IJ FAU - van Heyningen, Veronica AU - van Heyningen V