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Phosphorylation of the RNA-binding protein Dazl by MAPKAP kinase 2 regulates spermatogenesis
Journal article   Open access   Peer reviewed

Phosphorylation of the RNA-binding protein Dazl by MAPKAP kinase 2 regulates spermatogenesis

Patrick A Williams, Michael S Krug, Emily A McMillan, Jasmine D Peake, Tara L Davis, Simon Cocklin and Todd I Strochlic
Molecular biology of the cell, v 27(15), pp 2341-2350
01 Aug 2016
DOI: https://doi.org/10.1091/mbc.E15-11-0773
PMID: 27280388
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1091/mbc.e15-11-0773View
Published, Version of Record (VoR)CC BY-NC-SA V4.0,  Open

Abstract

Animals Drosophila - metabolism Gene Expression Germ Cells - metabolism Humans Intracellular Signaling Peptides and Proteins - metabolism Male p38 Mitogen-Activated Protein Kinases - metabolism Phosphorylation Protein-Serine-Threonine Kinases - metabolism RNA - metabolism RNA Recognition Motif Proteins RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Spermatogenesis - genetics Spermatogenesis - physiology Testis - metabolism
Developing male germ cells are exquisitely sensitive to environmental insults such as heat and oxidative stress. An additional characteristic of these cells is their unique dependence on RNA-binding proteins for regulating posttranscriptional gene expression and translational control. Here we provide a mechanistic link unifying these two features. We show that the germ cell-specific RNA-binding protein deleted in azoospermia-like (Dazl) is phosphorylated by MAPKAP kinase 2 (MK2), a stress-induced protein kinase activated downstream of p38 MAPK. We demonstrate that phosphorylation of Dazl by MK2 on an evolutionarily conserved serine residue inhibits its interaction with poly(A)-binding protein, resulting in reduced translation of Dazl-regulated target RNAs. We further show that transgenic expression of wild-type human Dazl but not a phosphomimetic form in the Drosophila male germline can restore fertility to flies deficient in boule, the Drosophila orthologue of human Dazl. These results illuminate a novel role for MK2 in spermatogenesis, expand the repertoire of RNA-binding proteins phosphorylated by this kinase, and suggest that signaling by the p38-MK2 pathway is a negative regulator of spermatogenesis via phosphorylation of Dazl.

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Cell Biology
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