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Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in

A Lespagnol1, D Duflaut, C Beekman

  • 1Laboratoire de Biotechnologie et Pharmacologie génétique Appliquée (LBPA), Ecole Normale Supérieure, Cachan, France.

Cell Death and Differentiation
|July 12, 2008
PubMed

Insights

Tumor suppressor-activated pathway 6 (TSAP6) is crucial for exosome production. TSAP6 deficiency in mice leads to anemia and impaired exosome secretion, highlighting its role in cellular communication.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • TSAP6 (Steap3) is a p53 target gene regulating protein secretion, including TCTP, linked to tumor reversion.
  • TSAP6 is a glycosylated protein localized in the trans-Golgi network, endosomal-vesicular compartment, and cytoplasmic membrane.

Purpose of the Study:

  • To investigate the physiological function of TSAP6 in exosome biogenesis and secretion.
  • To determine the role of TSAP6 in cellular processes affected by exosome regulation, such as anemia and transferrin receptor downregulation.

Main Methods:

  • Generation and analysis of TSAP6-deficient mice.
  • Biochemical and cellular analysis of TSAP6-null cells.
  • Investigation of the DNA damage-induced p53-dependent exosomal secretory pathway.

Main Results:

  • TSAP6-deficient mice exhibit microcytic anemia with abnormal reticulocyte maturation and impaired transferrin receptor downregulation.
  • Exosome production is severely compromised in TSAP6-null cells.
  • The DNA damage-induced p53-dependent nonclassical exosomal secretory pathway is abrogated in TSAP6-null cells.

Conclusions:

  • TSAP6 is essential for exosome formation and secretion.
  • TSAP6 plays a critical role in regulating exosome-dependent cellular processes, including transferrin receptor downregulation.
  • This study provides the first genetic evidence that exosome formation is tightly controlled by TSAP6.

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