Phosphatidylserine is a marker for axonal debris engulfment but its exposure can be decoupled from degeneration

Cell Death Dis. 2018 Nov 2;9(11):1116. doi: 10.1038/s41419-018-1155-z.


Apoptotic cells expose Phosphatidylserine (PS), that serves as an "eat me" signal for engulfing cells. Previous studies have shown that PS also marks degenerating axonsduring developmental pruning or in response to insults (Wallerian degeneration), but the pathways that control PS exposure on degenerating axons are largely unknown. Here, we used a series of in vitro assays to systematically explore the regulation of PS exposure during axonal degeneration. Our results show that PS exposure is regulated by the upstream activators of axonal pruning and Wallerian degeneration. However, our investigation of signaling further downstream revealed divergence between axon degeneration and PS exposure. Importantly, elevation of the axonal energetic status hindered PS exposure, while inhibition of mitochondrial activity caused PS exposure, without degeneration. Overall, our results suggest that the levels of PS on the outer axonal membrane can be dissociated from the degeneration process and that the axonal energetic status plays a key role in the regulation of PS exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Armadillo Domain Proteins / deficiency
  • Armadillo Domain Proteins / genetics
  • Axotomy
  • Biomarkers / metabolism
  • Cytoskeletal Proteins / deficiency
  • Cytoskeletal Proteins / genetics
  • Embryo, Mammalian
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Gene Expression
  • Mice
  • Mice, Knockout
  • Microfluidic Analytical Techniques
  • Nerve Growth Factor / pharmacology
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / genetics
  • Phosphatidylserines / metabolism
  • Phosphatidylserines / pharmacology*
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / pathology
  • Tissue Culture Techniques
  • Vincristine / pharmacology
  • Wallerian Degeneration / genetics
  • Wallerian Degeneration / metabolism*
  • bcl-2-Associated X Protein / deficiency
  • bcl-2-Associated X Protein / genetics


  • Armadillo Domain Proteins
  • Bax protein, mouse
  • Biomarkers
  • Cytoskeletal Proteins
  • Phosphatidylserines
  • SARM1 protein, mouse
  • bcl-2-Associated X Protein
  • Vincristine
  • Adenosine Triphosphate
  • Nerve Growth Factor