Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

p21-activated kinase 1 activity is required for histone H3 Ser10 phosphorylation and chromatin condensation in mouse oocyte meiosis

Nana Zhang A * , Xiuhong Li B * , Xiaoyun Liu A , Yan Cao A , Dandan Chen A , Xiaoyu Liu A , Qian Wang A , Juan Du A , Jing Weng C D and Wei Ma A D
+ Author Affiliations
- Author Affiliations

A Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.

B Biospecimen and Clinical Data Repository, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

C Experimental Center for Basic Medical Teaching, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.

D Corresponding authors. Emails: mawei1026@ccmu.edu.cn; wengjing@ccmu.edu.cn

Reproduction, Fertility and Development 29(7) 1287-1296 https://doi.org/10.1071/RD16026
Submitted: 13 January 2016  Accepted: 6 April 2016   Published: 11 May 2016

Abstract

p21-activated kinase 1 (Pak1) is essential for a variety of cellular events, including gene transcription, cytoskeletal organisation, cell proliferation and apoptosis. Pak1 is activated upon autophosphorylation on many amino residues; in particular, phosphorylation on Thr423 maintains maximal Pak1 activation. In the present study we investigated the protein expression, subcellular localisation and function of Pak1 phosphorylated on Thr423 (pPak1Thr423) in mouse oocytes. pPak1Thr423 was detected upon meiotic resumption and localised on the condensing chromatin. Thr423 phosphorylation was markedly suppressed by the Pak1 ATP-competitive inhibitor PF-3758309, but not by the allosteric inhibitors IPA-3 (2.5 μM and 10 μM) (1, 1′-dithiobis-2-naphthalenol) and TAT-PAK18 (10 μM), which prevent the binding of Pak1 to its upstream activators GTPase Cdc42/Rac and Pak-interacting exchange factor (PIX), respectively, implying that Pak1 activation may be independent of GTPase and PIX in oocyte meiosis. Inhibition of Pak1 activation concomitantly restrained histone H3 phosphorylation on Ser10 and consequently inhibited chromatin condensation; however, this phenotype was reversed by concomitant administration of the Pak1 activator FTY720. The changes in the pattern of expression of phosphorylated extracellular signal-regulated kinase 1/2 in response to PF-3758309 or FTY720 were the same as seen for pPak1Thr423. These results show that activated Pak1 regulates chromatin condensation by promoting H3 Ser10 phosphorylation in oocytes after the resumption of meiotic progression.

Additional keywords: Cdc42, chromosome separation, FTY720, germinal vesicle (GV), meiotic resumption, PF3758309, PIX.


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