Phosphorylation of the RNA-binding protein Dazl by MAPKAP kinase 2 regulates spermatogenesis
| Autor: | Patrick A. Williams, Jasmine D. Peake, Michael S. Krug, Simon Cocklin, Todd I. Strochlic, Emily A. McMillan, Tara L. Davis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male endocrine system Transgene p38 mitogen-activated protein kinases Gene Expression RNA-binding protein Biology Protein Serine-Threonine Kinases p38 Mitogen-Activated Protein Kinases 03 medical and health sciences DAZL 0302 clinical medicine Gene expression Testis Animals Humans Phosphorylation Protein kinase A Spermatogenesis Molecular Biology Kinase Intracellular Signaling Peptides and Proteins RNA-Binding Proteins Cell Biology Molecular biology 3. Good health 030104 developmental biology Germ Cells RNA Recognition Motif Proteins RNA Brief Reports Drosophila 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Developing male germ cells are exquisitely sensitive to stress and rely on RNA-binding proteins for posttranscriptional gene expression. Phosphorylation of the germ cell–specific RNA-binding protein deleted in azoospermia-like (Dazl) by the stress-activated protein kinase MK2 is a negative regulator of spermatogenesis. 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. |
| Databáze: | OpenAIRE |
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