Spatiotemporal control of epithelial remodeling by regulated myosin phosphorylation

被引:97
作者
Kasza, Karen E. [1 ,2 ]
Farrell, Dene L. [1 ,2 ]
Zallen, Jennifer A. [1 ,2 ]
机构
[1] Howard Hughes Med Inst, New York, NY 10065 USA
[2] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
PLANAR CELL POLARITY; LIGHT-CHAIN PHOSPHORYLATION; RHO-ASSOCIATED KINASE; NEURAL-TUBE CLOSURE; CONVERGENT EXTENSION; TISSUE MORPHOGENESIS; ACTOMYOSIN NETWORK; NONMUSCLE MYOSIN; AXIS ELONGATION; DROSOPHILA;
D O I
10.1073/pnas.1400520111
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Spatiotemporally regulated actomyosin contractility generates the forces that drive epithelial cell rearrangements and tissue remodeling. Phosphorylation of the myosin II regulatory light chain (RLC) promotes the assembly of myosin monomers into active contractile filaments and is an essential mechanism regulating the level of myosin activity. However, the effects of phosphorylation on myosin localization, dynamics, and function during epithelial remodeling are not well understood. In Drosophila, planar polarized myosin contractility is required for oriented cell rearrangements during elongation of the body axis. We show that regulated myosin phosphorylation influences spatial and temporal properties of contractile behavior at molecular, cellular, and tissue length scales. Expression of myosin RLC variants that prevent or mimic phosphorylation both disrupt axis elongation, but have distinct effects at the molecular and cellular levels. Unphosphorylatable RLC produces fewer, slower cell rearrangements, whereas phosphomimetic RLC accelerates rearrangement and promotes higher-order cell interactions. Quantitative live imaging and biophysical approaches reveal that both phosphovariants reduce myosin planar polarity and mechanical anisotropy, altering the orientation of cell rearrangements during axis elongation. Moreover, the localized myosin activator Rho-kinase is required for spatially regulated myosin activity, even when the requirement for phosphorylation is bypassed by the expression of phosphomimetic myosin RLC. These results indicate that myosin phosphorylation influences both the level and the spatiotemporal regulation of myosin activity, linking molecular properties of myosin activity to tissue morphogenesis.
引用
收藏
页码:11732 / 11737
页数:6
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