Importin β Is a Mitotic Target of the Small GTPase Ran in Spindle Assembly

Nachury, Maxence V.; Maresca, Thomas J.; Salmon, W. D.; Waterman‐Storer, Clare M.; Heald, Rebecca; Weis, Karsten

doi:10.1016/s0092-8674(01)00194-5

Cited by 368 publications

(311 citation statements)

References 59 publications

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“…The Ran gradient controls spindle morphogenesis through the regulation of many spindle assembly factors, such as the chromatin-driven MT-nucleating proteins TPX2 (Gruss et al, 2001) and NuSAP (Ribbeck et al, 2006), the spindle pole organizing factor NuMA (Nachury et al, 2001;Wiese et al, 2001), the K-fiber-binding protein HURP (Koffa et al, 2006;Sillje et al, 2006), the mRNA export factor Rae1 (Blower et al, 2005), the tumor suppressor BRCA1 (Joukov et al, 2006), and many others. Because of the complexity of various Ran substrates, we were unable to establish a direct link between Ran regulation and Kinesin-14 function in spindle assembly in somatic cells.…”

Section: The Activity Of Kinesin-14s In Spindle Morphologymentioning

confidence: 99%

Kinesin-14 Family Proteins HSET/XCTK2 Control Spindle Length by Cross-Linking and Sliding Microtubules

Cai

Weaver

Ems-McClung

et al. 2009

MBoC

171

196

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Kinesin-14 family proteins are minus-end directed motors that cross-link microtubules and play key roles during spindle assembly. We showed previously that the Xenopus Kinesin-14 XCTK2 is regulated by Ran via the association of a bipartite NLS in the tail of XCTK2 with importin ␣/␤, which regulates its ability to cross-link microtubules during spindle formation. Here we show that mutation of the nuclear localization signal (

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Section: The Activity Of Kinesin-14s In Spindle Morphologymentioning

confidence: 99%

Kinesin-14 Family Proteins HSET/XCTK2 Control Spindle Length by Cross-Linking and Sliding Microtubules

Cai

Weaver

Ems-McClung

et al. 2009

MBoC

171

196

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“…A large family of transport receptors, the karyopherin/importin-b (Kapb) family of receptors, is responsible for selective recognition of the vast majority of cargoes, as well as the physical translocation of the cargoes through NPCs (14). There are more than 20 family members in mammals (15)(16)(17)(18)(19). Although sequence identity between family members is low, Kapb receptors all assume a similar overall structure consisting largely of helical repeats, called HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A, and the yeast PI3-kinase TOR1) repeats (20).…”

Section: Overview Of Nucleocytoplasmic Transportmentioning

confidence: 99%

Nuclear localization signals and human disease

McLane

Corbett

2009

IUBMB Life

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SummaryIn eukaryotic cells, the physical separation of the genetic material in the nucleus from the translation and signaling machinery in the cytoplasm by the nuclear envelope creates a requirement for a mechanism through which macromolecules can enter or exit the nucleus as necessary. Nucleocytoplasmic transport involves the specific recognition of cargo molecules by transport receptors in one compartment followed by the physical relocation of that cargo into the other compartment through regulated pores that perforate the nuclear envelope. The recognition of protein cargoes by their transport receptors occurs via amino acid sequences in cargo proteins called nuclear targeting signals. Both nuclear import and export of proteins are highly regulated processes that control, not only what cargo can enter and/or exit the nucleus, but also when in the cell cycle and in what cell type, the cargo can be transported. Deregulation of the nuclear transport of specific cargoes has been linked to numerous cancers and developmental disorders highlighting the importance of understanding the mechanisms underlying nucleocytoplasmic transport and particularly the modulation of the specific interactions between transporter receptors and nuclear targeting signals within target cargo proteins.2009 IUBMB IUBMB Life, 61(7): [697][698][699][700][701][702][703][704][705][706] 2009

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“…Some of these proteins play a critical role in a centrosomeindependent spindle assembly pathway mediated by the Ran GTPase (see Dasso, 2002) including NuMA (Nachury et al, 2001;Wiese et al, 2001) and TPX-2 (Gruss et al, 2001). This is in contrast with pericentrin, which seems to be critical for assembly of mitotic asters but not Ran-mediated asters.…”

Section: Other Proteins Involved In Centrosomal ␥ Turc Anchoring and mentioning

confidence: 99%

Mitosis-specific Anchoring of γ Tubulin Complexes by Pericentrin Controls Spindle Organization and Mitotic Entry

Zimmerman

Sillibourne

Rosa

et al. 2004

MBoC

268

255

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Microtubule nucleation is the best known function of centrosomes. Centrosomal microtubule nucleation is mediated primarily by ␥ tubulin ring complexes (␥ TuRCs). However, little is known about the molecules that anchor these complexes to centrosomes. In this study, we show that the centrosomal coiled-coil protein pericentrin anchors ␥ TuRCs at spindle poles through an interaction with ␥ tubulin complex proteins 2 and 3 (GCP2/3). Pericentrin silencing by small interfering RNAs in somatic cells disrupted ␥ tubulin localization and spindle organization in mitosis but had no effect on ␥ tubulin localization or microtubule organization in interphase cells. Similarly, overexpression of the GCP2/3 binding domain of pericentrin disrupted the endogenous pericentrin-␥ TuRC interaction and perturbed astral microtubules and spindle bipolarity. When added to Xenopus mitotic extracts, this domain uncoupled ␥ TuRCs from centrosomes, inhibited microtubule aster assembly, and induced rapid disassembly of preassembled asters. All phenotypes were significantly reduced in a pericentrin mutant with diminished GCP2/3 binding and were specific for mitotic centrosomal asters as we observed little effect on interphase asters or on asters assembled by the Ran-mediated centrosome-independent pathway. Additionally, pericentrin silencing or overexpression induced G2/antephase arrest followed by apoptosis in many but not all cell types. We conclude that pericentrin anchoring of ␥ tubulin complexes at centrosomes in mitotic cells is required for proper spindle organization and that loss of this anchoring mechanism elicits a checkpoint response that prevents mitotic entry and triggers apoptotic cell death. INTRODUCTIONThe centrosome is the primary microtubule-organizing center in animal cells. At the centrosome core is a pair of barrel-shaped microtubule assemblies, the centrioles (Doxsey, 2001). Centrioles are capable of self-assembly (Marshall et al., 2001;Khodjakov et al., 2002) and can serve as templates for recruitment and organization of the surrounding pericentriolar matrix (Bobinnec et al., 1998;Kirkham et al., 2003). The pericentriolar material or centrosome matrix contains a high proportion of coiled coil proteins and is the site of microtubule nucleation. Within the matrix are large protein complexes of ␥ tubulin and associated proteins that have a ring-like structure and mediate the nucleation of microtubules called ␥ tubulin ring complexes or ␥ TuRCs (Moritz et al., 1995a;Zheng et al., 1995). Other proteins may share the ability to nucleate microtubules because centrosomes can organize microtubules in the absence of functional ␥ tubulin (Sampaio et al., 2001;Strome et al., 2001;Hannak et al., 2002).During cell cycle progression, centrosomes "mature" by recruiting additional ␥ TuRCs and several other proteins, resulting in an increase in the nucleation capacity of the centrosome (reviewed in Blagden and Glover, 2003). However, we still know very little about proteins that directly anchor ␥ TuRCs to centrosomes in vertebrate cells. ...

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Importin β Is a Mitotic Target of the Small GTPase Ran in Spindle Assembly

Cited by 368 publications

References 59 publications

Kinesin-14 Family Proteins HSET/XCTK2 Control Spindle Length by Cross-Linking and Sliding Microtubules

Kinesin-14 Family Proteins HSET/XCTK2 Control Spindle Length by Cross-Linking and Sliding Microtubules

Nuclear localization signals and human disease

Mitosis-specific Anchoring of γ Tubulin Complexes by Pericentrin Controls Spindle Organization and Mitotic Entry

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