Thymosin β4 is involved in stabilin-2-mediated apoptotic cell engulfment

Abstract 

Stabilin-2 was recently identified as a novel receptor for membrane phosphatidylserine of apoptotic cells. To identify proteins that were candidates for stabilin-2 cytoplasmic domain binding, we screened a human spleen cDNA library using the yeast two-hybrid system. We found that thymosin β4 interacts with the stabilin-2 cytoplasmic domain and is co-localized with stabilin-2 at the phagocytic cup. Knockdown of thymosin β4 significantly decreased the phagocytic activity of stabilin-2, whereas overexpression of thymosin β4 increased this activity. Additionally, amino acids 2504–2514 of stabilin-2 cytoplasmic domain were found to be responsible for the interaction with thymosin β4. Taken together, these results suggest that thymosin β4 is a downstream molecule of stabilin-2 that plays a role in stabilin-2-mediated cell corpse clearance.

Structured summary

Abbreviations: PS, phosphatidylserine, RBCs, red blood cells, LDL, low-density lipoprotein, AGE, advanced glycation end, GST, glutathione S-transferase, GFP, green fluorescent protein, siRNA, small interfering RNA, FITC, fluorecein-5-isothiocyanate, DIC, differential interference contrast, ILK, integrin linked kinase, ABPs, actin-binding proteins

Keywords: Stabilin-2, Thymosin β4, Phagocytosis, Yeast two-hybrid analysis