PUBLICATION
Myosin light chain kinase regulates cell polarization independently of membrane tension or Rho kinase
- Authors
- Lou, S.S., Diz-Muñoz, A., Weiner, O.D., Fletcher, D.A., Theriot, J.A.
- ID
- ZDB-PUB-150429-2
- Date
- 2015
- Source
- The Journal of cell biology 209: 275-88 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Blotting, Western
- Cell Adhesion
- Cell Membrane/enzymology
- Cell Membrane/pathology*
- Cell Movement
- Cell Polarity*
- Cell Shape
- Cells, Cultured
- Corneal Keratocytes/cytology
- Corneal Keratocytes/metabolism
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism*
- Flow Cytometry
- Myosin-Light-Chain Kinase/genetics
- Myosin-Light-Chain Kinase/metabolism*
- Myosins/metabolism*
- Phosphorylation
- Pseudopodia/metabolism
- RNA, Messenger/genetics
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Zebrafish/growth & development
- Zebrafish/metabolism*
- rho-Associated Kinases/genetics
- rho-Associated Kinases/metabolism*
- PubMed
- 25918227 Full text @ J. Cell Biol.
Citation
Lou, S.S., Diz-Muñoz, A., Weiner, O.D., Fletcher, D.A., Theriot, J.A. (2015) Myosin light chain kinase regulates cell polarization independently of membrane tension or Rho kinase. The Journal of cell biology. 209:275-88.
Abstract
Cells polarize to a single front and rear to achieve rapid actin-based motility, but the mechanisms preventing the formation of multiple fronts are unclear. We developed embryonic zebrafish keratocytes as a model system for investigating establishment of a single axis. We observed that, although keratocytes from 2 d postfertilization (dpf) embryos resembled canonical fan-shaped keratocytes, keratocytes from 4 dpf embryos often formed multiple protrusions despite unchanged membrane tension. Using genomic, genetic, and pharmacological approaches, we determined that the multiple-protrusion phenotype was primarily due to increased myosin light chain kinase (MLCK) expression. MLCK activity influences cell polarity by increasing myosin accumulation in lamellipodia, which locally decreases protrusion lifetime, limiting lamellipodial size and allowing for multiple protrusions to coexist within the context of membrane tension limiting protrusion globally. In contrast, Rho kinase (ROCK) regulates myosin accumulation at the cell rear and does not determine protrusion size. These results suggest a novel MLCK-specific mechanism for controlling cell polarity via regulation of myosin activity in protrusions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping