Active Ran regulates anillin function during cytokinesis

Beaudet, Daniel; Akhshi, Tara; Phillipp, Julia; Law, Christopher J.; Piekny, Alisa

doi:10.1091/mbc.e17-04-0253

Cited by 29 publications

(73 citation statements)

References 52 publications

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“…We found the NLS of anillin is required for its localization and function during cytokinesis (Beaudet et al, 2017). In addition, anillin contains a RhoA-binding domain (RBD) required for cortical recruitment, and we found that the RBD autoinhibits the adjacent NLS-containing C2 domain.…”

Section: Introductionmentioning

confidence: 82%

“…Since anillin crosslinks key components of the cell during cytokinesis, understanding its molecular regulation can provide insight to how cytokinesis is regulated. In particular, the C-terminus of anillin contains a RhoA-GTP binding domain (RBD), a neighboring C2 domain, and a Pleckstrin Homology (PH) domain, which coordinate its localization through 1) binding to active RhoA, 2) binding to phospholipids, importins and/or microtubules via the C2 domain, and 3) binding to phospholipids and/or septins via the PH domain (Oegema et al, 2000;Piekny and Glotzer, 2008;Piekny and Maddox, 2010;Liu et al, 2012;van Oostende Triplet et al, 2014;Sun et al, 2015;Beaudet et al, 2017). However, which of these interactions is crucial for anillin function and how they are coordinated is not clear.…”

Section: Introductionmentioning

confidence: 99%

“…von Dassow et al, 2009;Cabernard et al, 2010;Schenk et al, 2010;Sedzinski et al, 2011;Kiyomitsu and Cheeseman, 2013;Zanin et al, 2013;Rodrigues et al, 2015;Beaudet et al, 2017).…”

Section: Introductionunclassified

“…Several studies showed that the membrane-localization of this complex is crucial for Ect2's GEF 4 2013; Samwer et al, 2013;Beaudet et al, 2017). This mechanism senses chromatin position to ensure that the polar body or contractile ring are properly positioned.…”

Section: Introductionmentioning

confidence: 99%

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Intramolecular regulation of anillin during cytokinesis

Beaudet

Pham

Skaik

et al. 2019

Preprint

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Cytokinesis occurs by the ingression of an actomyosin ring that cleaves a cell into two daughters. This process is tightly controlled to avoid aneuploidy, and we previously showed that active Ran coordinates ring positioning with chromatin. Active Ran is high around chromatin, and forms an inverse gradient to cargo-bound importins. We found that the ring component anillin contains an NLS that binds to importin and is required for its function. Anillin contains a RhoAbinding domain (RBD), which we revealed autoinhibits the adjacent NLS-containing C2 domain.Here, we show that active RhoA relieves inhibition of the C2 domain. Furthermore, FRAP experiments show that the NLS regulates anillin's cortical properties, supporting feedback to the RBD. Indeed, mutations that disrupt the interface between the RBD and C2 domain disrupt anillin's localization and function. Thus, active RhoA induces a conformational change that increases accessibility to the C2 domain, which is maintained by importin-binding for recruitment to the equatorial cortex. activity vs. spindle localization and the role of microtubules remains to be clarified (Frenette et al., 2012;Lakomtsev et al.

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Section: Introductionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

“…von Dassow et al, 2009;Cabernard et al, 2010;Schenk et al, 2010;Sedzinski et al, 2011;Kiyomitsu and Cheeseman, 2013;Zanin et al, 2013;Rodrigues et al, 2015;Beaudet et al, 2017).…”

Section: Introductionunclassified

Section: Introductionmentioning

confidence: 99%

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Intramolecular regulation of anillin during cytokinesis

Beaudet

Pham

Skaik

et al. 2019

Preprint

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“…ANLN , a conserved multi‐domain protein, is a prime candidate for functioning in scaffolding and organizing the cytoskeleton due to its many protein–protein interactions. In humans, ANLN is required for cortical polarity and cytokinesis (Beaudet, Akhshi, Phillipp, Law, & Piekny, ). Considering that human ANLN is normally degraded after mitotic exit and sequestered in the nucleus during interphase, its over‐expression may disturb these normal regulatory mechanisms, freeing ANLN to affect the actomyosin cytoskeleton during events outside of cytokinesis, including, cell motility which promotes cell differentiation and the spatial programing of the inner, middle and outer structures of the ears (Noden & Van de Water, ; Zhang & Maddox, ).…”

Section: Discussionmentioning

confidence: 99%

Identification of ANLN as a new likely pathogenic gene of branchio‐otic syndrome in a three‐generation Chinese family

Deng

Liu

Xia

et al. 2018

Molec Gen & Gen Med

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Background Branchio‐oto‐renal (BOR) syndrome is one of the most common autosomal dominant hearing loss syndromes and features clinical and genetic heterogeneity. When there is no renal deformity, this disease can also be called branchio‐otic (BO) syndrome. Though many genes have been reported, there are still many BO syndrome‐related genes to be identified. To identify a hitherto unknown candidate gene causing BO syndrome in a three‐generation Chinese family, clinical, genetic, and functional analyses were employed. Methods Whole‐exome sequencing (WES) was conducted in three affected family members and two unaffected family members. PCR‐Sanger sequencing was performed in all of the family members for segregation analysis and verification of the candidate variants. PCR‐Sanger sequencing was also employed in 150 healthy people to examine the variants. In silico analysis was used to predict possible changes in the protein structure that may affect the phenotype. Results We identified a heterozygous missense variant in ANLN : NM_018685.4: c.G1105A; NP_061155.2: p.G369R that segregated in the pedigree with an autosomal dominant pattern. No variant was found in the 150 controls and normal family members at this site. The variant c.G1105A was located in a highly conserved F‐actin binding site. The amino acid residue at position 369 in the ANLN protein was highly conserved across different species. Conclusion In this study, we identified, for the first time, a heterozygous missense variant in ANLN (NM_018685.4: c.G1105A; NP_061155.2: p.G369R) that is likely to be a candidate causative gene of BO syndrome in a specific Chinese family.

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Regulation and Assembly of Actomyosin Contractile Rings in Cytokinesis and Cell Repair

Dekraker

Boucher

Mandato

2018

The Anatomical Record

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Cytokinesis and single‐cell wound repair both involve contractile assemblies of filamentous actin (F‐actin) and myosin II organized into characteristic ring‐like arrays. The assembly of these actomyosin contractile rings (CRs) is specified spatially and temporally by small Rho GTPases, which trigger local actin polymerization and myosin II contractility via a variety of downstream effectors. We now have a much clearer view of the Rho GTPase signaling cascade that leads to the formation of CRs, but some factors involved in CR positioning, assembly, and function remain poorly understood. Recent studies show that this regulation is multifactorial and goes beyond the long‐established Ca2+‐dependent processes. There is substantial evidence that the Ca2+‐independent changes in cell shape, tension, and plasma membrane composition that characterize cytokinesis and single‐cell wound repair also regulate CR formation. Elucidating the regulation and mechanistic properties of CRs is important to our understanding of basic cell biology and holds potential for therapeutic applications in human disease. In this review, we present a primer on the factors influencing and regulating CR positioning, assembly, and contraction as they occur in a variety of cytokinetic and single‐cell wound repair models. Anat Rec, 301:2051–2066, 2018. © 2018 Wiley Periodicals, Inc.

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Active Ran regulates anillin function during cytokinesis

Cited by 29 publications

References 52 publications

Intramolecular regulation of anillin during cytokinesis

Intramolecular regulation of anillin during cytokinesis

Identification of ANLN as a new likely pathogenic gene of branchio‐otic syndrome in a three‐generation Chinese family

Regulation and Assembly of Actomyosin Contractile Rings in Cytokinesis and Cell Repair

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