Complementary Functions for the Ran Gradient During Division

Overview

Journal Small GTPases

Specialties Biochemistry
Cell Biology

Date 2020 Feb 5

PMID 32013678

Citations 10

Authors

Imge Ozugergin

Alisa Piekny

Affiliations

Soon will be listed here.

Abstract

The Ran pathway has a well-described function in nucleocytoplasmic transport, where active Ran dissociates importin/karyopherin-bound cargo containing a nuclear localization signal (NLS) in the nucleus. As cells enter mitosis, the nuclear envelope breaks down and a gradient of active Ran forms where levels are highest near chromatin. This gradient plays a crucial role in regulating mitotic spindle assembly, where active Ran binds to and releases importins from NLS-containing spindle assembly factors. An emerging theme is that the Ran gradient also regulates the actomyosin cortex for processes including polar body extrusion during meiosis, and cytokinesis. For these events, active Ran could play an inhibitory role, where importin-binding may help promote or stabilize a conformation or interaction that favours the recruitment and function of cortical regulators. For either spindle assembly or cortical polarity, the gradient of active Ran determines the extent of importin-binding, the effects of which could vary for different proteins.

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References

Trieselmann N, Armstrong S, Rauw J, Wilde A . Ran modulates spindle assembly by regulating a subset of TPX2 and Kid activities including Aurora A activation. J Cell Sci. 2003; 116(Pt 23):4791-8. DOI: 10.1242/jcs.00798. View

Wu X, Suetsugu S, Cooper L, Takenawa T, Guan J . Focal adhesion kinase regulation of N-WASP subcellular localization and function. J Biol Chem. 2003; 279(10):9565-76. DOI: 10.1074/jbc.M310739200. View

Yi K, Unruh J, Deng M, Slaughter B, Rubinstein B, Li R . Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3-complex-driven cytoplasmic streaming in mouse oocytes. Nat Cell Biol. 2011; 13(10):1252-8. PMC: 3523671. DOI: 10.1038/ncb2320. View

Gadde S, Heald R . Mechanisms and molecules of the mitotic spindle. Curr Biol. 2004; 14(18):R797-805. DOI: 10.1016/j.cub.2004.09.021. View

Kimura M, Imamoto N . Biological significance of the importin-β family-dependent nucleocytoplasmic transport pathways. Traffic. 2014; 15(7):727-48. DOI: 10.1111/tra.12174. View

von Dassow G, Verbrugghe K, Miller A, Sider J, Bement W . Action at a distance during cytokinesis. J Cell Biol. 2009; 187(6):831-45. PMC: 2806324. DOI: 10.1083/jcb.200907090. View

Petronczki M, Glotzer M, Kraut N, Peters J . Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev Cell. 2007; 12(5):713-25. DOI: 10.1016/j.devcel.2007.03.013. View

Yuce O, Piekny A, Glotzer M . An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol. 2005; 170(4):571-82. PMC: 2171506. DOI: 10.1083/jcb.200501097. View

Bennabi I, Terret M, Verlhac M . Meiotic spindle assembly and chromosome segregation in oocytes. J Cell Biol. 2016; 215(5):611-619. PMC: 5147004. DOI: 10.1083/jcb.201607062. View

10.

Brownlee C, Heald R . Importin α Partitioning to the Plasma Membrane Regulates Intracellular Scaling. Cell. 2019; 176(4):805-815.e8. PMC: 6368448. DOI: 10.1016/j.cell.2018.12.001. View

11.

Giesecke A, Stewart M . Novel binding of the mitotic regulator TPX2 (target protein for Xenopus kinesin-like protein 2) to importin-alpha. J Biol Chem. 2010; 285(23):17628-35. PMC: 2878527. DOI: 10.1074/jbc.M110.102343. View

12.

Chan C, Jans D . Synergy of importin alpha recognition and DNA binding by the yeast transcriptional activator GAL4. FEBS Lett. 1999; 462(1-2):221-4. DOI: 10.1016/s0014-5793(99)01515-x. View

13.

Green R, Paluch E, Oegema K . Cytokinesis in animal cells. Annu Rev Cell Dev Biol. 2012; 28:29-58. DOI: 10.1146/annurev-cellbio-101011-155718. View

14.

Su L, Agati J, Parsons S . p190RhoGAP is cell cycle regulated and affects cytokinesis. J Cell Biol. 2003; 163(3):571-82. PMC: 2173658. DOI: 10.1083/jcb.200308007. View

15.

Forbes D, Travesa A, Nord M, Bernis C . Nuclear transport factors: global regulation of mitosis. Curr Opin Cell Biol. 2015; 35:78-90. PMC: 4529785. DOI: 10.1016/j.ceb.2015.04.012. View

16.

Lange A, Mills R, Lange C, Stewart M, Devine S, Corbett A . Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem. 2006; 282(8):5101-5. PMC: 4502416. DOI: 10.1074/jbc.R600026200. View

17.

Hara T, Abe M, Inoue H, Yu L, Veenstra T, Kang Y . Cytokinesis regulator ECT2 changes its conformation through phosphorylation at Thr-341 in G2/M phase. Oncogene. 2005; 25(4):566-78. DOI: 10.1038/sj.onc.1209078. View

18.

Xu L, Massague J . Nucleocytoplasmic shuttling of signal transducers. Nat Rev Mol Cell Biol. 2004; 5(3):209-19. DOI: 10.1038/nrm1331. View

19.

Suetsugu S, Takenawa T . Translocation of N-WASP by nuclear localization and export signals into the nucleus modulates expression of HSP90. J Biol Chem. 2003; 278(43):42515-23. DOI: 10.1074/jbc.M302177200. View

20.

Burdyniuk M, Callegari A, Mori M, Nedelec F, Lenart P . F-Actin nucleated on chromosomes coordinates their capture by microtubules in oocyte meiosis. J Cell Biol. 2018; 217(8):2661-2674. PMC: 6080919. DOI: 10.1083/jcb.201802080. View