posted on 2016-07-16, 00:00authored byX. Liu, T. Yang, K. Suzuki, S. Tsukita, M. Ishii, S. Zhou, G. Wang
Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in
the correct direction, and engulfing the bacteria. How neutrophils establish and precisely
orient this polarity toward pathogens remains unclear. Here we report that in resting
neutrophils, the ERM (ezrin, radixin, and moesin) protein moesin in its active form (phosphorylated
and membrane bound) prevented cell polarization by inhibiting the small
GTPases Rac, Rho, and Cdc42. Attractant-induced activation of myosin phosphatase
deactivated moesin at the prospective leading edge to break symmetry and establish polarity.
Subsequent translocation of moesin to the trailing edge confined the formation of a
prominent pseudopod directed toward pathogens and prevented secondary pseudopod
formation in other directions. Therefore, both moesin-mediated inhibition and its localized
deactivation by myosin phosphatase are essential for neutrophil polarization and effective
neutrophil tracking of pathogens
Funding
This work was supported in part by grants from the US National Institutes of
Health (HL095716, HL077806, and AI033503), Chinese Academic of Sciences (KSCXW-R-66),
and Natural Science Foundation of China (30630037).