PTENα promotes neutrophil chemotaxis through regulation of cell deformability.

Neutrophils are a major component of immune defense and are recruited through neutrophil chemotaxis in response to invading pathogens. However, the molecular mechanism that controls neutrophil chemotaxis remains unclear. Here, we report that PTENα, the first isoform identified in the PTEN family, regulates neutrophil deformability and promotes chemotaxis of neutrophils. A high level of PTENα is detected in neutrophils and lymphoreticular tissues. Homozygous deletion of PTENα impairs chemoattractant-induced migration of neutrophils. We show that PTENα physically interacts with cell membrane cross-linker moesin through its FERM domain and dephosphorylates moesin at Thr558, which disrupts the association of filamentous actin with the plasma membrane and subsequently induces morphologic changes in neutrophil pseudopodia. These results demonstrate that PTENα acts as a phosphatase of moesin and modulates neutrophil-mediated host immune defense. We propose that PTENα signaling is a potential target for the treatment of infections and immune diseases.