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PMID:18159085

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Citation

Xiong, W, Chen, Y, Wang, H, Wang, H, Wu, H, Lu, Q and Han, D (2008) Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction 135:77-87

Abstract

The apoptotic spermatogenic cells and residual bodies are phagocytosed and degraded by Sertoli cells during spermatogenesis. The mechanisms of this process are largely unknown. Here, we demonstrate that Gas6 and its receptors, the Tyro 3 subfamily of receptor tyrosine kinases (RTKs; Tyro 3, Axl, and Mer), regulate the phagocytic function of Sertoli cells. The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. The Sertoli cells lacking Mer showed a 35% reduction in phagocytosis of apoptotic spermatogenic cells when compared with wild-type (WT) controls, whereas the Sertoli cells lacking Tyro 3 or Axl exhibited phagocytic activity comparable with the controls. Notably, the Sertoli cells lacking all three members of the Tyro 3 RTK subfamily showed a dramatic decrease in phagocytic ability of 7.6-fold when compared with WT Sertoli cells. The deficiency in phagocytosis by the triple-mutant Sertoli cells was due to the deficit in binding of the Sertoli cells to apoptotic germ cells. These findings suggest that Mer is responsible for triggering phagocytosis of apoptotic spermatogenic cells by Sertoli cells and that Tyro 3, Axl, and Mer participate in recognizing and binding apoptotic germ cells by Sertoli cells in a redundant manner. Gas6 is a functional ligand of the Tyro 3 RTK subfamily in mediating phagocytic ability of Sertoli cells.

Links

PubMed Online version:10.1530/REP-07-0287

Keywords

Animals; Apoptosis; Cells, Cultured; Intercellular Signaling Peptides and Proteins/genetics; Male; Mice; Mice, Knockout; Phagocytosis/physiology; Receptor Protein-Tyrosine Kinases/genetics; Sertoli Cells/metabolism; Spermatogenesis/physiology; Spermatozoa/cytology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TYRO3

acts_upstream_of_or_within

GO:0043277: apoptotic cell clearance

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1347244
MGI:MGI:96965

P

Seeded From UniProt

complete

MOUSE:TYRO3

involved_in

GO:0043277: apoptotic cell clearance

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q60805

P

Seeded From UniProt

complete

MOUSE:UFO

acts_upstream_of_or_within

GO:0043277: apoptotic cell clearance

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104294
MGI:MGI:96965

P

Seeded From UniProt

complete

MOUSE:UFO

involved_in

GO:0043277: apoptotic cell clearance

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q60805

P

Seeded From UniProt

complete

MOUSE:GAS6

acts_upstream_of_or_within

GO:0043277: apoptotic cell clearance

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MERTK

acts_upstream_of_or_within

GO:0043277: apoptotic cell clearance

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104294
MGI:MGI:1347244

P

Seeded From UniProt

complete

MOUSE:MERTK

involved_in

GO:0043277: apoptotic cell clearance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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