Kdm3a lysine demethylase is an Hsp90 client required for cytoskeletal rearrangements during spermatogenesis
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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.
Kasioulis , I , Syred , H M , Tate , P , Finch , A , Shaw , J , Seawright , A , Fuszard , M A , Botting , C H , Shirran , S , Adams , I R , Jackson , I J , van Heyningen , V & Yeyati , P L 2014 , ' Kdm3a lysine demethylase is an Hsp90 client required for cytoskeletal rearrangements during spermatogenesis ' Molecular Biology of the Cell , vol 25 , no. 8 , pp. 1216-1233 . DOI: 10.1091/mbc.E13-08-0471
Molecular Biology of the Cell
© 2014 Kasioulis et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
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