During unilateral furrow ingression, one side of the cytokinetic ring (leading edge) ingresses before the opposite side (lagging edge). Anillin mediates unilateral furrowing during cytokinesis in the one-cell C. elegans zygote by limiting myosin II accumulation in the ring. Here, we address the role of anillin in this process and show that anillin inhibits not only the accumulation of myosin II but also of other RhoA effectors by binding and blocking the RhoA effector site. The interaction between the anillin’s RhoA-binding domain (RBD) and active RhoA is enhanced by the disordered linker region and differentially regulated at the leading and lagging edge, which together results in asymmetric RhoA signaling and accumulation of myosin II. In summary, we discover a RhoA GEF- and GAP-independent mechanism, where RhoA activity is limited by anillin binding to the RhoA effector site. Spatial fine-tuning of anillin’s inhibitory role on RhoA signaling enables unilateral furrow ingression and contributes to animal development.
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2 June 2025
Article|
April 22 2025
Anillin mediates unilateral furrowing during cytokinesis by limiting RhoA binding to its effectors
Mikhail Lebedev
,
Mikhail Lebedev
(Formal analysis, Investigation, Methodology, Visualization, Writing - review & editing)
1Department Biologie,
Friedrich-Alexander-Universität Erlangen-Nürnberg
, Erlangen, Germany
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Fung-Yi Chan
,
Fung-Yi Chan
(Funding acquisition, Investigation, Methodology, Writing - review & editing)
3
i3S - Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto
, Porto, Portugal
4
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto
, Porto, Portugal
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Elisabeth Rackles
,
Elisabeth Rackles
(Investigation, Writing - review & editing)
2Department Biology II,
Ludwig-Maximilians University Munich
, Munich, Germany
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Jennifer Bellessem
,
Jennifer Bellessem
(Investigation)
2Department Biology II,
Ludwig-Maximilians University Munich
, Munich, Germany
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Tamara Mikeladze-Dvali
,
Tamara Mikeladze-Dvali
(Conceptualization, Funding acquisition, Supervision, Writing - review & editing)
2Department Biology II,
Ludwig-Maximilians University Munich
, Munich, Germany
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Ana Xavier Carvalho
,
Ana Xavier Carvalho
(Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing)
3
i3S - Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto
, Porto, Portugal
4
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto
, Porto, Portugal
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Esther Zanin
(Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing)
1Department Biologie,
Friedrich-Alexander-Universität Erlangen-Nürnberg
, Erlangen, Germany
2Department Biology II,
Ludwig-Maximilians University Munich
, Munich, Germany
Correspondence to Esther Zanin: [email protected]
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Mikhail Lebedev
Formal analysis, Investigation, Methodology, Visualization, Writing - review & editing
1Department Biologie,
Friedrich-Alexander-Universität Erlangen-Nürnberg
, Erlangen, Germany
Fung-Yi Chan
Funding acquisition, Investigation, Methodology, Writing - review & editing
3
i3S - Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto
, Porto, Portugal
4
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto
, Porto, Portugal
Elisabeth Rackles
Investigation, Writing - review & editing
2Department Biology II,
Ludwig-Maximilians University Munich
, Munich, Germany
Jennifer Bellessem
Investigation
2Department Biology II,
Ludwig-Maximilians University Munich
, Munich, Germany
Tamara Mikeladze-Dvali
Conceptualization, Funding acquisition, Supervision, Writing - review & editing
2Department Biology II,
Ludwig-Maximilians University Munich
, Munich, Germany
Ana Xavier Carvalho
Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing
3
i3S - Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto
, Porto, Portugal
4
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto
, Porto, Portugal
Esther Zanin
Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing
1Department Biologie,
Friedrich-Alexander-Universität Erlangen-Nürnberg
, Erlangen, Germany
2Department Biology II,
Ludwig-Maximilians University Munich
, Munich, Germany
Correspondence to Esther Zanin: [email protected]
Disclosures: The authors declare no competing interests exist.
Received:
May 31 2024
Revision Received:
February 10 2025
Accepted:
March 18 2025
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funding
Funder(s):
Deutsche Forschungsgemeinschaft
- Award Id(s): ZA619/3,MI1867/1-1
Funder(s):
European Research Council
- Award Id(s): 640553
Funder(s):
Fundação para a Ciência e a Tecnologia
- Award Id(s): UIDB/04293/2020,DL 57/2016/CP1355/CT0013
Funder(s):
Scientific Employment Stimulus
- Award Id(s): CEECIND/01967/2017,2023.14140.TENURE.0139
Funder(s):
National Institutes of Health
- Award Id(s): P40 OD010440
© 2025 Lebedev et al.
2025
Lebedev et al.
This article is distributed under the terms as described at https://rupress.org/pages/terms102024/.
J Cell Biol (2025) 224 (6): e202405182.
Article history
Received:
May 31 2024
Revision Received:
February 10 2025
Accepted:
March 18 2025
Connected Content
Citation
Mikhail Lebedev, Fung-Yi Chan, Elisabeth Rackles, Jennifer Bellessem, Tamara Mikeladze-Dvali, Ana Xavier Carvalho, Esther Zanin; Anillin mediates unilateral furrowing during cytokinesis by limiting RhoA binding to its effectors. J Cell Biol 2 June 2025; 224 (6): e202405182. doi: https://doi.org/10.1083/jcb.202405182
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