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两种具有不同定位控制的 RhoGEF 同工型在不对称细胞分裂过程中控制沟的位置。

Two RhoGEF isoforms with distinct localisation control furrow position during asymmetric cell division.

机构信息

CNRS, UMR5095, University of Bordeaux, Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607, Pessac, France.

CNRS, UMR5095, University of Bordeaux, Institut de Biologie et Génétique Cellulaire, 1 rue Camille Saint-Saëns, 33077, Bordeaux, France.

出版信息

Nat Commun. 2023 Jun 2;14(1):3209. doi: 10.1038/s41467-023-38912-9.

Abstract

Cytokinesis partitions cellular content between daughter cells. It relies on the formation of an acto-myosin contractile ring, whose constriction induces the ingression of the cleavage furrow between the segregated chromatids. Rho1 GTPase and its RhoGEF (Pbl) are essential for this process. However, how Rho1 is regulated to sustain furrow ingression while maintaining correct furrow position remains poorly defined. Here, we show that during asymmetric division of Drosophila neuroblasts, Rho1 is controlled by two Pbl isoforms with distinct localisation. Spindle midzone- and furrow-enriched Pbl-A focuses Rho1 at the furrow to sustain efficient ingression, while Pbl-B pan-plasma membrane localization promotes the broadening of Rho1 activity and the subsequent enrichment of myosin on the entire cortex. This enlarged zone of Rho1 activity is critical to adjust furrow position, thereby preserving correct daughter cell size asymmetry. Our work highlights how the use of isoforms with distinct localisation makes an essential process more robust.

摘要

胞质分裂将细胞内容物分配到子细胞中。它依赖于肌动球蛋白收缩环的形成,该收缩环的收缩诱导分离的染色单体之间的分裂沟的内陷。Rho1 GTPase 和其 RhoGEF(Pbl)对于这个过程是必不可少的。然而,Rho1 如何被调节以维持沟的内陷,同时保持正确的沟位置仍然定义不明确。在这里,我们表明在果蝇神经母细胞的不对称分裂期间,Rho1 受到两种具有不同定位的 Pbl 同工型的控制。纺锤体中部和沟富含的 Pbl-A 将 Rho1 集中在沟处以维持有效的内陷,而 Pbl-B 全质膜定位促进 Rho1 活性的扩大,并随后在整个皮质上富集肌球蛋白。这种扩大的 Rho1 活性区对于调整沟的位置至关重要,从而保持正确的子细胞大小不对称性。我们的工作强调了如何使用具有不同定位的同工型使一个基本过程更加稳健。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a19/10238489/3d61d40f394e/41467_2023_38912_Fig1_HTML.jpg

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