Internal feedback circuits among MEX-5, MEX-6, and PLK-1 maintain faithful patterning in the Caenorhabditis elegans embryo

被引:0
作者
Vaudano, Alexandre Pierre [1 ]
Schwager, Francoise [1 ]
Gotta, Monica [1 ]
Barbieri, Sofia [1 ]
机构
[1] Univ Geneva, Fac Med, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland
基金
瑞士国家科学基金会;
关键词
reaction-diffusion; RNA binding proteins; MEX-5; MEX-6; PLK-1; polarity feedback loops; Monte Carlo simulations; POLO-LIKE KINASE; PAR PROTEINS; RNA-BINDING; CELL POLARITY; ASYMMETRY; ESTABLISHMENT; GRADIENTS; POLARIZATION;
D O I
10.1073/pnas.2407517121
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
Proteins become asymmetrically distributed in the one- cell Caenorhabditis elegans embryo thanks to reaction-diffusion mechanisms that are often entangled in complex feedback loops. Cortical polarity drives the enrichment of the RNA- binding proteins MEX-5 and MEX-6 in the anterior cytoplasm through concentration gradients. MEX-5 and MEX-6 promote the patterning of other cytoplasmic factors, including that of the anteriorly enriched mitotic polo- like kinase PLK-1, but also contribute to proper cortical polarity. The gradient of MEX-5 forms through a differential- diffusion mechanism. How MEX-6 establishes a gradient and how MEX-5 and MEX-6 regulate cortical polarity is not known. Here, we reveal that the two MEX proteins develop concentration asymmetries via similar mechanisms, but despite their strong sequence homology, they differ in terms of how their concentration gradients are regulated. We find that PLK-1 promotes the enrichment of MEX-5 and MEX-6 at the anterior through different circuits: PLK-1 influences the MEX-5 gradient indirectly by regulating cortical polarity while it modulates the formation of the gradient of MEX-6 through its physical interaction with the protein. We thus propose a model in which PLK-1 mediates protein circuitries between MEX-5, MEX-6, and cortical proteins to faithfully establish and maintain polarity.
引用
收藏
页数:11
相关论文
共 52 条
[11]  
Cuenca A. A., Schetter A., Aceto D., Kemphues K., Seydoux G., Polarization of the C. elegans zygote proceeds via distinct establishment and maintenance phases, Development, 130, pp. 1255-1265, (2003)
[12]  
Goehring N. W., Et al., Polarization of PAR proteins by advective triggering of a pattern-forming system, Science, 334, pp. 1137-1141, (2011)
[13]  
Sailer A., Anneken A., Li Y., Lee S., Munro E., Dynamic opposition of clustered proteins stabilizes cortical polarity in the C. elegans zygote, Dev. Cell, 35, pp. 131-142, (2015)
[14]  
Dickinson D. J., Schwager F., Pintard L., Gotta M., Goldstein B., A single-cell biochemistry approach reveals PAR complex dynamics during cell polarization, Dev. Cell, 42, pp. 416-434, (2017)
[15]  
Illukkumbura R., Et al., Design principles for selective polarization of PAR proteins by cortical flows, J. Cell Biol, 222, (2023)
[16]  
Chang Y., Dickinson D. J., A particle size threshold governs diffusion and segregation of PAR-3 during cell polarization, Cell Rep, 39, (2022)
[17]  
Hird S. N., White J. G., Cortical and cytoplasmic flow polarity in early embryonic cells of Caenorhabditis elegans, J. Cell Biol, 121, pp. 1343-1355, (1993)
[18]  
Goehring N. W., Hoege C., Grill S. W., Hyman A. A., PAR proteins diffuse freely across the anterior- posterior boundary in polarized C. elegans embryos, J. Cell Biol, 193, pp. 583-594, (2011)
[19]  
Goehring N. W., PAR polarity: From complexity to design principles, Exp. Cell Res, 328, pp. 258-266, (2014)
[20]  
Tostevin F., Howard M., Modeling the establishment of PAR protein polarity in the one-cell C. elegans embryo, Biophys. J, 95, pp. 4512-4522, (2008)