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

Ioannis Kasioulis, Heather M. Syred, Peri Tate, Andrew Finch, Joseph Shaw, Anne Seawright, Matthew Alexander Fuszard, Catherine H. Botting, Sally Shirran, Ian R. Adams, Ian J. Jackson, Veronica van Heyningen, Patricia L. Yeyati*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
3 Downloads (Pure)

Abstract

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 beta-actin and gamma-tubulin. Kdm3a is therefore a multifunctional Hsp90 client protein that participates directly in the regulation of cytoskeletal components.

Original languageEnglish
Pages (from-to)1216-1233
Number of pages18
JournalMolecular Biology of the Cell
Volume25
Issue number8
DOIs
Publication statusPublished - 15 Apr 2014

Keywords

  • Histone demethylase
  • Gene-expression
  • In-vivo
  • Epigenetic regulation
  • Cell-proliferation
  • Spermatid head
  • Stem-cells
  • Jmjd1a
  • Actin
  • Jhdm2a

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