A chimerical phagocytosis model reveals the recruitment by Sertoli cells of autophagy for the degradation of ingested illegitimate substrates

Autophagy. 2013 May;9(5):653-66. doi: 10.4161/auto.23839. Epub 2013 Feb 25.


Phagocytosis and autophagy are typically dedicated to degradation of substrates of extrinsic and intrinsic origins respectively. Although overlaps between phagocytosis and autophagy were reported, the use of autophagy for ingested substrate degradation by nonprofessional phagocytes has not been described. Blood-separated tissues use their tissue-specific nonprofessional phagocytes for homeostatic phagocytosis. In the testis, Sertoli cells phagocytose spermatid residual bodies produced during germ cell differentiation. In the retina, pigmented epithelium phagocytoses shed photoreceptor tips produced during photoreceptor renewal. Spermatid residual bodies and shed photoreceptor tips are phosphatidylserine-exposing substrates. Activation of the tyrosine kinase receptor MERTK, which is implicated in phagocytosis of phosphatidylserine-exposing substrates, is a common feature of Sertoli and retinal pigmented epithelial cell phagocytosis. The major aim of our study was to investigate to what extent phagocytosis by Sertoli cells may be tissue specific. We analyzed in Sertoli cell cultures that were exposed to either spermatid residual bodies (legitimate substrates) or retina photoreceptor outer segments (illegitimate substrates) the course of the main phagocytosis stages. We show that whereas substrate binding and ingestion stages occur similarly for legitimate or illegitimate substrates, the degradation of illegitimate but not of legitimate substrates triggers autophagy as evidenced by the formation of double-membrane wrapping, MAP1LC3A-II/LC3-II clustering, SQSTM1/p62 degradation, and by marked changes in ATG5, ATG9 and BECN1/Beclin 1 protein expression profiles. The recruitment by nonprofessional phagocytes of autophagy for the degradation of ingested cell-derived substrates is a novel feature that may be of major importance for fundamentals of both apoptotic substrate clearance and tissue homeostasis.

Keywords: MERTK tyrosine kinase; Sertoli cells; apoptotic substrates; autophagy; homeostatic phagocytosis; protein S; vitamin K-dependent factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Autophagy-Related Protein 5
  • Humans
  • Macrolides / pharmacology
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Models, Biological*
  • Myosin Type II / metabolism
  • Phagocytosis* / drug effects
  • Phosphorylation / drug effects
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • Pseudopodia / ultrastructure
  • Rats
  • Rats, Wistar
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Rod Cell Outer Segment / drug effects
  • Rod Cell Outer Segment / metabolism
  • Rod Cell Outer Segment / ultrastructure
  • Sertoli Cells / cytology*
  • Sertoli Cells / drug effects
  • Sertoli Cells / enzymology
  • Sertoli Cells / ultrastructure
  • c-Mer Tyrosine Kinase


  • Atg5 protein, rat
  • Autophagy-Related Protein 5
  • Macrolides
  • Microtubule-Associated Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • bafilomycin A1
  • Mertk protein, rat
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase
  • Myosin Type II