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ZFIN ID: ZDB-PUB-170214-297
The PAR complex controls the spatiotemporal dynamics of F-actin and the MTOC in directionally migrating leukocytes
Crespo, C.L., Vernieri, C., Keller, P.J., Garrè, M., Bender, J.R., Wittbrodt, J., Pardi, R.
Date: 2014
Source: Journal of Cell Science 127: 4381-95 (Journal)
Registered Authors: Keller, Philipp
Keywords: 3D Migration, Cell polarity, Cytoskeleton, Inflammation, Leukocyte, PAR complex
MeSH Terms:
  • Actin Cytoskeleton/metabolism
  • Actins/metabolism
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Animals, Genetically Modified
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism*
  • Cell Movement*
  • Cell Polarity/genetics
  • Cells, Cultured
  • Leukocytes/physiology*
  • Microtubule-Organizing Center/physiology*
  • Multiprotein Complexes/genetics
  • Mutation/genetics
  • Oryzias
  • Protein Kinase C/genetics
  • Protein Kinase C/metabolism*
  • Protein Transport
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • rho-Associated Kinases/metabolism
PubMed: 25179599 Full text @ J. Cell Sci.
Inflammatory cells acquire a polarized phenotype to migrate towards 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. However, there is no evidence that myeloid cells use PAR signaling to migrate vectorially in three-dimensional (3D) environments in vivo. Using genetically encoded bioprobes and high-resolution live imaging, we reveal the existence of F-actin oscillations in the trailing edge and constant repositioning of the microtubule organizing center (MTOC) to direct leukocyte migration in wounded medaka fish larvae (Oryzias latipes). Genetic manipulation in live myeloid cells demonstrates that the catalytic activity of aPKC and the regulated interaction with PAR-3 and PAR-6 are required for consistent F-actin oscillations, MTOC perinuclear mobility, aPKC repositioning and wound-directed migration upstream of Rho kinase (also known as ROCK or ROK) activation. We propose that the PAR complex coordinately controls cytoskeletal changes affecting both the generation of traction force and the directionality of leukocyte migration to sites of injury.