Annexin III implicated in the microglial response to motor nerve injury

Abstract To identify proteins implicated in peripheral nerve regeneration, we performed two‐dimensional polyacrylamide gel electrophoresis and subsequent mass spectrometry analysis using nerve‐injured hypoglossal nuclei of rat. We have identified annexin III (ANX III/ANX A3) as an induced protein after rat hypoglossal nerve injury. ANX III is known as a Ca 2+ ‐dependent phospholipid‐binding protein, but its physiological function is mostly unknown. By in situ hybridization and immunohistochemistry, we demonstrated that ANX III expression was induced specifically in activated (axotomy‐stimulated) microglia after nerve injury. ANX III was the most prominent ANX expressed in microglia of the major ANX family members (ANX I‐VI). Hybridization signals for other ANX mRNAs (II, IV, V, and VI) were mainly observed in neuronal cells, and no significant hybridization signal for ANX I mRNA was detected in hypoglossal nuclei. In cultured microglia, ATP treatment induced ANX III translocation to the ruffling membrane where F‐actin was accumulated. Further in vitro studies revealed that ANX III was not secreted and had F‐actin binding activity in a Ca 2+ ‐dependent manner. These results suggest that ANX III may be a Ca 2+ ‐dependent mediator between phospholipids and F‐actin in microglia stimulated by peripheral nerve injury. © 2006 Wiley‐Liss, Inc.