The PAR complex controls the spatiotemporal dynamics of F-actin and the MTOC in directionally migrating leukocytes

Abstract

Inflammatory cells acquire a polarized phenotype to migrate toward sites of infection or injury. A conserved polarity complex comprising PAR-3, PAR-6, and atypical protein kinase C (aPKC) relays extracellular polarizing cues to control cytoskeletal and signaling networks affecting morphological and functional polarization. Yet, there is no evidence that myeloid cells use PAR signaling to migrate vectorially in 3D environments in vivo. Using genetically-encoded bioprobes and high-resolution live imaging we revealed the existence of F-actin oscillations in the trailing edge and constant MTOC repositioning to direct leukocyte migration in wounded medaka fish larvae. Genetic manipulation in live myeloid cells demonstrated that the catalytic activity of aPKC and the regulated interaction with PAR-3/PAR-6 are required for consistent F-actin oscillations, MTOC perinuclear mobility, aPKC repositioning and wound-directed migration upstream of Rho-kinase/ROCK/ROK activation. We propose that the PAR complex coordinately controls cytoskeletal changes affecting both traction force generation and directionality of leukocyte migration to sites of injury.