Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2012

The contribution of regulated nuclear transport to male fertility (#125)

Kate L Loveland 1 2 , Yoichi Miyamoto 1 , Julia C Young 2 , Gavin Higgins 1 , Arash Arjomand 1 , Chin L Wong 1 , Lynne Mayne 1 , Paul McMenamin 2 , David A Jans 1
  1. Biochemistry and Molecular Biology, Monash University, Melbourne, Australia
  2. Anatomy and Developmental Biology, Monash University, Melbourne, Australia

Regulated nucleocytoplasmic transport is of central importance to the fidelity of tightly regulated gene expression that is required for gametogenesis and adult fertility1 .  Our work has identified many aspects of protein transport between the cytoplasm and nucleus that are modulated throughout spermatogenesis.  We are now working to delineate the physiological importance of key molecules involved in this, with a particular focus on the importins/karyopherins.  Importin α (IMPα) proteins reside predominantly in the cytoplasm and are classically understood to function with an importinβ1 molecule to ferry cargo containing a nuclear localisation signal (NLS) into the nucleus. Non-transport functions for IMPα proteins are emerging; we recently showed that IMPα proteins act within the nucleus to regulate gene transcription. The Serine threonine kinase 35 (Stk35) transcript was singularly upregulated in HeLa cells exposed to cellular stress conditions that provoked IMPα nuclear accumulation2.  Remarkably, we had previously shown that IMPα4 is nuclear in spermatocytes and spermatids3, cells in which STK35 is transcribed.  This presentation will describe discoveries from our three new mouse strains which indicate that IMPα proteins not only selectively deliver essential cargo to the nucleus, but also directly modify cell fate through nuclear actions including transcriptional regulation and driving nuclear remodelling events spermatogenesis.

  1. Major, A.T, Whiley, P.A.F. and Loveland, K.L. (2011) Expression of nucleocytoplasmic transport machinery: Clues to regulation of spermatogenic development. Biochemica Biophysica Acta, Molecular Cell Research. 1813(9):1668-88.
  2. Yasuda, Y., Miyamoto, Y., Yamashiro, T., Asally, M., Masui, A., Wong, C., Loveland, K.L. and Yoneda, Y. 2011. Nuclear retention of importin α2 coordinates cell fate through changes in gene expression. EMBO Journal 31(1):83-94.
  3. Hogarth, C.A, Jans, D.A, and Loveland, K.L. (2007) Subcellular distribution of importins correlates with germ cell maturation. Dev. Dyn. 236:2311-20.