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有丝分裂期假复层上皮细胞变圆过程中的粘着连接重塑。

Adherens junction remodelling during mitotic rounding of pseudostratified epithelial cells.

机构信息

Epithelial Biology Laboratory, Francis Crick Institute, London, UK.

EMBL Australia, The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia.

出版信息

EMBO Rep. 2020 Apr 3;21(4):e49700. doi: 10.15252/embr.201949700. Epub 2020 Feb 7.

DOI:10.15252/embr.201949700
PMID:32030856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7132200/
Abstract

Epithelial cells undergo cortical rounding at the onset of mitosis to enable spindle orientation in the plane of the epithelium. In cuboidal epithelia in culture, the adherens junction protein E-cadherin recruits Pins/LGN/GPSM2 and Mud/NuMA to orient the mitotic spindle. In the pseudostratified columnar epithelial cells of Drosophila, septate junctions recruit Mud/NuMA to orient the spindle, while Pins/LGN/GPSM2 is surprisingly dispensable. We show that these pseudostratified epithelial cells downregulate E-cadherin as they round up for mitosis. Preventing cortical rounding by inhibiting Rho-kinase-mediated actomyosin contractility blocks downregulation of E-cadherin during mitosis. Mitotic activation of Rho-kinase depends on the RhoGEF ECT2/Pebble and its binding partners RacGAP1/MgcRacGAP/CYK4/Tum and MKLP1/KIF23/ZEN4/Pav. Cell cycle control of these Rho activators is mediated by the Aurora A and B kinases, which act redundantly during mitotic rounding. Thus, in Drosophila pseudostratified epithelia, disruption of adherens junctions during mitosis necessitates planar spindle orientation by septate junctions to maintain epithelial integrity.

摘要

上皮细胞在有丝分裂开始时经历皮质圆形化，以实现纺锤体在上皮平面上的定向。在培养的立方上皮中，黏着连接蛋白 E-钙黏蛋白招募 Pins/LGN/GPSM2 和 Mud/NuMA 来定向有丝分裂纺锤体。在果蝇的假复层柱状上皮细胞中，隔膜连接招募 Mud/NuMA 来定向纺锤体，而 Pins/LGN/GPSM2 出人意料地是可有可无的。我们表明，这些假复层上皮细胞在为有丝分裂而变圆时下调 E-钙黏蛋白。通过抑制 Rho-激酶介导的肌动球蛋白收缩来阻止皮质圆形化，可阻止 E-钙黏蛋白在有丝分裂期间下调。Rho-激酶的有丝分裂激活依赖于 RhoGEF ECT2/Pebble 及其结合伴侣 RacGAP1/MgcRacGAP/CYK4/Tum 和 MKLP1/KIF23/ZEN4/Pav。这些 Rho 激活物的细胞周期控制由 Aurora A 和 B 激酶介导，它们在有丝分裂圆形化过程中冗余地发挥作用。因此，在果蝇假复层上皮中，有丝分裂期间黏着连接的破坏需要通过隔膜连接来维持上皮完整性，从而实现平面纺锤体定向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/297d/7132200/ddfe0f72c171/EMBR-21-e49700-g013.jpg
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2
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3
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4
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5
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6
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