Musashi-1 maintains blood-testis barrier structure during spermatogenesis and regulates stress granule formation upon heat stress

Mol Biol Cell. 2015 May 15;26(10):1947-56. doi: 10.1091/mbc.E14-11-1497. Epub 2015 Feb 25.

Abstract

In mouse testes, Musashi-1 (Msi-1) was predominantly expressed in the cytoplasm and nuclei of Sertoli cells. Here we demonstrate that knockdown of Msi-1 in Sertoli cells altered the levels and distribution of blood-testis barrier (BTB)-associated proteins. Moreover, Msi-1 knockdown in vivo disrupted BTB functional structure and spermatogenesis. In addition, we report a novel role of Msi-1 in regulating Sertoli cells survival following heat-induced injury. Endogenous Msi-1 protein in heat-treated Sertoli cells was recruited to stress granules. The formation of stress granules was considerably disrupted, and apoptosis was significantly up-regulated in Msi-1-knockdown Sertoli cells after heat treatment. p-ERK1/2 acted downstream of stress granule formation, and inhibition of p-ERK1/2 signaling triggered Sertoli cell apoptosis upon heat stress. In conclusion, we demonstrate that Msi-1 is critical for constructing a functional BTB structure and maintaining spermatogenesis. We also note a role for Msi-1 in regulating Sertoli cell fate following heat-induced injury, likely through the induction of stress granule formation and subsequent activation of p-ERK1/2 signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Blood-Testis Barrier / anatomy & histology
  • Blood-Testis Barrier / metabolism
  • Blood-Testis Barrier / physiology*
  • Cytoplasmic Granules / metabolism*
  • Gene Knockdown Techniques
  • Heat-Shock Response*
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology*
  • Sertoli Cells / metabolism
  • Sertoli Cells / physiology*
  • Spermatogenesis / physiology*

Substances

  • Msi1h protein, mouse
  • Nerve Tissue Proteins
  • RNA-Binding Proteins