RRC ID 74746
著者 di Pietro F, Osswald M, De Las Heras JM, Cristo I, López-Gay J, Wang Z, Pelletier S, Gaugué I, Leroy A, Martin C, Morais-de-Sá E, Bellaïche Y.
タイトル Systematic analysis of RhoGEF/GAP localizations uncovers regulators of mechanosensing and junction formation during epithelial cell division.
ジャーナル Curr Biol
Abstract Cell proliferation is central to epithelial tissue development, repair, and homeostasis. During cell division, small RhoGTPases control both actomyosin dynamics and cell-cell junction remodeling to faithfully segregate the genome while maintaining tissue polarity and integrity. To decipher the mechanisms of RhoGTPase spatiotemporal regulation during epithelial cell division, we generated a transgenic fluorescently tagged library for the 48 Drosophila Rho guanine exchange factors (RhoGEFs) and GTPase-activating proteins (GAPs), and we systematically characterized their endogenous distributions by time-lapse microscopy. Therefore, we unveiled candidate regulators of the interplay between actomyosin and junctional dynamics during epithelial cell division. Building on these findings, we established that the conserved RhoGEF Cysts and RhoGEF4 play sequential and distinct roles to couple cytokinesis with de novo junction formation. During ring contraction, Cysts via Rho1 participates in the neighbor mechanosensing response, promoting daughter-daughter cell membrane juxtaposition in preparation to de novo junction formation. Subsequently and upon midbody formation, RhoGEF4 via Rac acts in the dividing cell to ensure the withdrawal of the neighboring cell membranes, thus controlling de novo junction length and cell-cell arrangements upon cytokinesis. Altogether, our findings delineate how the RhoGTPases Rho and Rac are locally and temporally activated during epithelial cytokinesis, highlighting the RhoGEF/GAP library as a key resource to understand the broad range of biological processes regulated by RhoGTPases.
巻・号 33(5)
ページ 858-874.e7
公開日 2023-3-13
DOI 10.1016/j.cub.2023.01.028
PII S0960-9822(23)00062-3
PMID 36917931
PMC PMC10017266
MeSH Actomyosin* / metabolism Animals Cell Division Cytokinesis Drosophila Epithelial Cells* Rho Guanine Nucleotide Exchange Factors / genetics Rho Guanine Nucleotide Exchange Factors / metabolism
IF 9.601
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