Differential contribution of the MTOR and MNK pathways to the regulation of mRNA translation in meiotic and postmeiotic mouse male germ cells

Valeria Messina, Annarita Di Di Sauro, Simona Pedrotti, Laura Adesso, Alessia Latina, Raffaele Geremia, Pellegrino Rossi, Claudio Sette

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Translation of stored mRNAs accounts for protein synthesis during the transcriptionally inactive stages of spermatogenesis. A key step in mRNA translation is the assembly of the initiation complex EIF4F, which is regulated by the MTOR (mammalian target of rapamycin) and MNK1/2 (MAP kinase-interacting kinase 1 and 2) pathways. We investigated the expression and activity of regulatory proteins of these pathways in male germ cells at different stages of differentiation. All translation factors analyzed were expressed in germ cells throughout spermatogenesis. However, while EIF4G and PABP1 (poly[A]-binding protein 1) were more abundant in postmeiotic cells, MTOR and its target EIF4EBP1 (4E-BP1) decreased steadily during spermatogenesis. In vivo labeling showed that pachytene spermatocytes display higher rates of protein synthesis, which are partially dependent on MTOR and MNK activity. By contrast, haploid spermatids are characterized by lower levels of protein synthesis, which are independent of the activity of these pathways. Accordingly, MTOR and MNK activity enhanced formation of the EIF4F complex in pachytene spermatocytes but not in round spermatids. Moreover, external cues differentially modulated the activity of these pathways in meiotic and haploid cells. Heat shock decreased MTOR and MNK activity in pachytene spermatocytes, whereas round spermatids were much less sensitive. On the other hand, treatment with the phosphatase inhibitor okadaic acid activated MTOR and MNK in both cell types. These results indicate that translational regulation is differentially dependent on the MTOR and MNK pathways in mouse spermatocytes and spermatids and suggest that the late stages of germ cell differentiation display constitutive assembly of the translation initiation complex.

Original languageEnglish
Pages (from-to)607-615
Number of pages9
JournalBiology of Reproduction
Volume83
Issue number4
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Protein Biosynthesis
Sirolimus
Germ Cells
Spermatocytes
Spermatids
Eukaryotic Initiation Factor-4F
Spermatogenesis
Haploidy
Eukaryotic Initiation Factor-4G
Proteins
MAP Kinase Kinase 2
Poly(A)-Binding Proteins
MAP Kinase Kinase 1
Stored Messenger RNA
Okadaic Acid
Phosphoric Monoester Hydrolases
Cues
Cell Differentiation
Shock
Hot Temperature

Keywords

  • Gamete biology
  • Kinases
  • Meiosis
  • MNK
  • mRNA translation
  • mRNA translational regulation
  • MTOR
  • RNA metabolism
  • Signal transduction
  • Spermatogenesis

ASJC Scopus subject areas

  • Cell Biology

Cite this

Differential contribution of the MTOR and MNK pathways to the regulation of mRNA translation in meiotic and postmeiotic mouse male germ cells. / Messina, Valeria; Di Sauro, Annarita Di; Pedrotti, Simona; Adesso, Laura; Latina, Alessia; Geremia, Raffaele; Rossi, Pellegrino; Sette, Claudio.

In: Biology of Reproduction, Vol. 83, No. 4, 10.2010, p. 607-615.

Research output: Contribution to journalArticle

Messina, Valeria ; Di Sauro, Annarita Di ; Pedrotti, Simona ; Adesso, Laura ; Latina, Alessia ; Geremia, Raffaele ; Rossi, Pellegrino ; Sette, Claudio. / Differential contribution of the MTOR and MNK pathways to the regulation of mRNA translation in meiotic and postmeiotic mouse male germ cells. In: Biology of Reproduction. 2010 ; Vol. 83, No. 4. pp. 607-615.
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AU - Di Sauro, Annarita Di

AU - Pedrotti, Simona

AU - Adesso, Laura

AU - Latina, Alessia

AU - Geremia, Raffaele

AU - Rossi, Pellegrino

AU - Sette, Claudio

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