Dissection of autophagy in human platelets

Autophagy. 2014 Apr;10(4):642-51. doi: 10.4161/auto.27832. Epub 2014 Jan 21.

Abstract

Continuous turnover of intracellular components by autophagy is necessary to preserve cellular homeostasis in all tissues. Despite recent advances in identifying autophagy-related genes and understanding the functions of autophagy in developmental and pathological conditions, so far, the role of autophagy in platelet, a specific anucleate cell type, is poorly understood. In this study, we showed that human platelets express the autophagy-related proteins ATG5, ATG7, and LC3. The same as in nucleated mammalian cells, autophagy was stimulated by cell starvation or the MTOR inhibitor rapamycin in a phosphatidylinositol 3-kinase (PtdIns3K)-dependent manner. Disruption of autophagic flux led to impairment of platelet aggregation and adhesion. Furthermore, Becn1 heterozygous knockout mice displayed a prolonged bleeding time and reduced platelet aggregation. These results suggest a potential role of autophagy in the regulation of platelet function, and imply that gene transcription may not be an essential prerequisite for adaptive autophagy.

Keywords: Beclin 1; autophagosome; autophagy; platelet; thrombus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy / physiology*
  • Beclin-1
  • Bleeding Time
  • Blood Platelets / cytology
  • Blood Platelets / metabolism*
  • Heterozygote
  • Humans
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • Transcriptional Activation / physiology

Substances

  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Becn1 protein, mouse
  • TOR Serine-Threonine Kinases