Microtubules ‘Rac and Rho’ in migrating neutrophils

Microtubules contribute to directed cell migration by positively regulating cell polarity. Previous work on isolated neutrophils showed that disruption of microtubules enhances migration but impairs directionality – presumably through the activation of Rho – but little is known with regard to how microtubules regulate neutrophil migration in 3D tissue environments in vivo. Here (p. 5702), Anna Huttenlocher and colleagues used the zebrafish system to study the role of microtubules in neutrophil migration in 3D in vivo. Interestingly, in contrast to findings of in vitro studies, they show the microtubule-organising centre to be positioned in front of the nucleus in motile neutrophils. The authors have previously shown that phosphoinositide-3 kinase (PI3K) regulates neutrophil motility and, in this work, they addressed the molecular details of PI3K signaling in this process. They demonstrate that microtubule disassembly induces neutrophil motility, at least in part, through the activation of both Rho and Rac in a manner that is independent of PI3K activity. The involvement of Rac is unexpected as, in other cell types, it is activated by microtubule polymerisation and not depolymerisation. Taken together, these results provide new insights into the role of microtubules in neutrophil migration in a living vertebrate, and also show that the motility of these migratory cells follows different rules than those established for other cell types.