Flotillin microdomains interact with the cortical cytoskeleton to control uropod formation and neutrophil recruitment

We studied the function of plasma membrane microdomains defined by the proteins flotillin 1 and flotillin 2 in uropod formation and neutrophil chemotaxis Flotillins become concentrated in the uropod of neutrophils after exposure to chemoattractants such as N formyl Met Leu-Phe (fMLP) Here, we show that mice lacking llotillin 1 do not have flotillin microdomains, and that recruitment of neutrophils toward fMLP in vivo is reduced in these mice Ex vivo, migration of neutrophils through a resistive matrix is reduced in the absence of flotillin microdomains, but the machinery required for sensing chemoattractant functions normally Flotillin microdomains specifically associate with myosin lla, and spectrins Both uropod formation and myosin Ila activity are compromised in flotillin 1 knockout neutrophils We con dude that the association between flotillin microdomains and cortical cytoskeleton has important functions during neutrophil migration, in uropod formation, and in the regulation of myosin Ila