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<p>Extracellular vesicles (EVs) are nano-sized, membrane-delimited, particles released by cells that carry signaling macromolecules. A major pathway of EV production is potentiated by neutral sphingomyelinase 2 (SMPD3/nSMAse2), an enzyme that generates ceramide from sphingomyelin. In our attempt to study this pathway in adipocytes of male mice, we discover that the elimination of SMPD3 from adipocytes in vivo triggers a signal to surrounding immune cell-like preadipocytes to release EVs that carry SMPD3 mRNA. This results in a widespread increase in SMPD3 mRNA in purified null adipocytes without a change in the transcripts of other enzymes involved in ceramide metabolism. These results point to a selective mechanism by which specific mRNA molecules are acquired from the microenvironment to a level that can restore expression of mRNA and protein in a cell that is depleted of the corresponding genetic information.</p>

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Adipocytes signal to recruit specific mRNAs from surrounding cells to restore expression deficits

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月11日

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  • Clair Crewe,
  • Christy M. Gliniak,
  • Toshiharu Onodera,
  • Shiuhwei Chen,
  • Jan-Bernd Funcke,
  • May-Yun Wang,
  • Snigdha Tiash,
  • Yun-Ling Pai,
  • Marjori Russo,
  • Saket Awadhesbhai Patel,
  • Ze Yu,
  • Yi-Cian Zheng,
  • Alex Larkin,
  • Chao Xing,
  • Laurent Gautron,
  • Chun-Kan Chen,
  • Chen Liu,
  • Philipp E. Scherer

摘要

Extracellular vesicles (EVs) are nano-sized, membrane-delimited, particles released by cells that carry signaling macromolecules. A major pathway of EV production is potentiated by neutral sphingomyelinase 2 (SMPD3/nSMAse2), an enzyme that generates ceramide from sphingomyelin. In our attempt to study this pathway in adipocytes of male mice, we discover that the elimination of SMPD3 from adipocytes in vivo triggers a signal to surrounding immune cell-like preadipocytes to release EVs that carry SMPD3 mRNA. This results in a widespread increase in SMPD3 mRNA in purified null adipocytes without a change in the transcripts of other enzymes involved in ceramide metabolism. These results point to a selective mechanism by which specific mRNA molecules are acquired from the microenvironment to a level that can restore expression of mRNA and protein in a cell that is depleted of the corresponding genetic information.