ZFIN ID: ZDB-PUB-190902-21
Coronin 1A depletion restores the nuclear stability and viability of Aip1/Wdr1-deficient neutrophils
Bowes, C., Redd, M., Yousfi, M., Tauzin, M., Murayama, E., Herbomel, P.
Date: 2019
Source: The Journal of cell biology   218(10): 3258-3271 (Journal)
Registered Authors: Bowes, Charnese, Herbomel, Philippe, Murayama, Emi, Redd, Michael, Tauzin, Muriel, Yousfi, Malika
Keywords: none
MeSH Terms:
  • 4-Butyrolactone/analogs & derivatives*
  • 4-Butyrolactone/deficiency
  • Animals
  • Cell Nucleus/metabolism*
  • Cell Survival
  • Microfilament Proteins/deficiency*
  • Neutrophils/cytology*
  • Neutrophils/metabolism*
  • Zebrafish
PubMed: 31471458 Full text @ J. Cell Biol.
ABSTRACT
Actin dynamics is central for cells, and especially for the fast-moving leukocytes. The severing of actin filaments is mainly achieved by cofilin, assisted by Aip1/Wdr1 and coronins. We found that in Wdr1-deficient zebrafish embryos, neutrophils display F-actin cytoplasmic aggregates and a complete spatial uncoupling of phospho-myosin from F-actin. They then undergo an unprecedented gradual disorganization of their nucleus followed by eruptive cell death. Their cofilin is mostly unphosphorylated and associated with F-actin, thus likely outcompeting myosin for F-actin binding. Myosin inhibition reproduces in WT embryos the nuclear instability and eruptive death of neutrophils seen in Wdr1-deficient embryos. Strikingly, depletion of the main coronin of leukocytes, coronin 1A, fully restores the cortical location of F-actin, nuclear integrity, viability, and mobility of Wdr1-deficient neutrophils in vivo. Our study points to an essential role of actomyosin contractility in maintaining the integrity of the nucleus of neutrophils and a new twist in the interplay of cofilin, Wdr1, and coronin in regulating F-actin dynamics.
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