Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Cell Scientists to Watch
    • First Person
    • Sign up for alerts
  • About us
    • About JCS
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Fast-track manuscripts
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • JCS Prize
    • Manuscript transfer network
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contact JCS
    • Subscriptions
    • Advertising
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in

Search

  • Advanced search
Journal of Cell Science
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Journal of Cell Science

  • Log in
Advanced search

RSS   Twitter  Facebook   YouTube  

  • Home
  • Articles
    • Accepted manuscripts
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Cell Scientists to Watch
    • First Person
    • Sign up for alerts
  • About us
    • About JCS
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Fast-track manuscripts
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • JCS Prize
    • Manuscript transfer network
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contact JCS
    • Subscriptions
    • Advertising
    • Feedback
Research Article
PP2A­-B55γ counteracts Cdk1 and regulates proper spindle orientation through the cortical dynein adaptor NuMA
Riya Keshri, Ashwathi Rajeevan, Sachin Kotak
Journal of Cell Science 2020 133: jcs243857 doi: 10.1242/jcs.243857 Published 31 July 2020
Riya Keshri
Department of Microbiology and Cell Biology, Indian Institute of Science, 560012 Bangalore, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ashwathi Rajeevan
Department of Microbiology and Cell Biology, Indian Institute of Science, 560012 Bangalore, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sachin Kotak
Department of Microbiology and Cell Biology, Indian Institute of Science, 560012 Bangalore, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sachin Kotak
  • For correspondence: sachinkotak@iisc.ac.in

Handling Editor: David Glover

  • Article
  • Figures & tables
  • Supp info
  • Info & metrics
  • PDF + SI
  • PDF
Loading

ABSTRACT

Proper orientation of the mitotic spindle is critical for accurate development and morphogenesis. In human cells, spindle orientation is regulated by the evolutionarily conserved protein NuMA, which interacts with dynein and enriches it at the cell cortex. Pulling forces generated by cortical dynein orient the mitotic spindle. Cdk1-mediated phosphorylation of NuMA at threonine 2055 (T2055) negatively regulates its cortical localization. Thus, only NuMA not phosphorylated at T2055 localizes at the cell cortex. However, the identity and the mechanism of action of the phosphatase complex involved in T2055 dephosphorylation remains elusive. Here, we characterized the PPP2CA-B55γ (PPP2R2C)–PPP2R1B complex that counteracts Cdk1 to orchestrate cortical NuMA for proper spindle orientation. In vitro reconstitution experiments revealed that this complex is sufficient for T2055 dephosphorylation. Importantly, we identified polybasic residues in NuMA that are critical for T2055 dephosphorylation, and for maintaining appropriate cortical NuMA levels for accurate spindle elongation. Furthermore, we found that Cdk1-mediated phosphorylation and PP2A-B55γ-mediated dephosphorylation at T2055 are reversible events. Altogether, this study uncovers a novel mechanism by which Cdk1 and its counteracting PP2A-B55γ complex orchestrate spatiotemporal levels of cortical force generators for flawless mitosis.

Footnotes

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: S.K.; Methodology: R.K., S.K.; Validation: R.K., A.R., S.K.; Formal analysis: R.K., A.R., S.K.; Investigation: R.K., S.K.; Resources: S.K.; Data curation: R.K., S.K.; Writing - original draft: S.K.; Writing - review & editing: R.K., A.R., S.K.; Visualization: S.K.; Supervision: S.K.; Project administration: S.K.; Funding acquisition: S.K.

  • Funding

    This work is supported by the Department of Biotechnology, Ministry of Science and Technology, India – Indian Institute of Science Partnership Program and by grants from The Wellcome Trust DBT India Alliance Fellowship (IA/I/15/2/502077 to S.K.). S.K. is a The Wellcome Trust DBT India Alliance Intermediate Fellow. Deposited in PMC for release after 6 months.

  • Supplementary information

    Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.243857.supplemental

  • Received January 9, 2020.
  • Accepted June 16, 2020.
  • © 2020. Published by The Company of Biologists Ltd
http://www.biologists.com/user-licence-1-1/
View Full Text

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$30.00 .

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Previous ArticleNext Article
Back to top
Previous ArticleNext Article

This Issue

Keywords

  • Cdk1
  • NuMA
  • PP2A
  • Dynein
  • Mitosis
  • Spindle orientation

 Download PDF

Email

Thank you for your interest in spreading the word on Journal of Cell Science.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
PP2A­-B55γ counteracts Cdk1 and regulates proper spindle orientation through the cortical dynein adaptor NuMA
(Your Name) has sent you a message from Journal of Cell Science
(Your Name) thought you would like to see the Journal of Cell Science web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Research Article
PP2A­-B55γ counteracts Cdk1 and regulates proper spindle orientation through the cortical dynein adaptor NuMA
Riya Keshri, Ashwathi Rajeevan, Sachin Kotak
Journal of Cell Science 2020 133: jcs243857 doi: 10.1242/jcs.243857 Published 31 July 2020
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Research Article
PP2A­-B55γ counteracts Cdk1 and regulates proper spindle orientation through the cortical dynein adaptor NuMA
Riya Keshri, Ashwathi Rajeevan, Sachin Kotak
Journal of Cell Science 2020 133: jcs243857 doi: 10.1242/jcs.243857 Published 31 July 2020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • RESULTS
    • DISCUSSION
    • MATERIALS AND METHODS
    • Acknowledgements
    • Footnotes
    • Peer review history
    • References
  • Figures & tables
  • Supp info
  • Info & metrics
  • PDF + SI
  • PDF

Related articles

Cited by...

More in this TOC section

  • Switching between blebbing and lamellipodia depends on the degree of non-muscle myosin II activity
  • Kindlin-2 promotes rear focal adhesion disassembly and directional persistence during cell migration
  • Histone chaperone APLF level dictates the implantation of mouse embryos
Show more RESEARCH ARTICLE

Similar articles

Other journals from The Company of Biologists

Development

Journal of Experimental Biology

Disease Models & Mechanisms

Biology Open

Advertisement

2020 at The Company of Biologists

Despite the challenges of 2020, we were able to bring a number of long-term projects and new ventures to fruition. While we look forward to a new year, join us as we reflect on the triumphs of the last 12 months.


Mole – The Corona Files

"This is not going to go away, 'like a miracle.' We have to do magic. And I know we can."

Mole continues to offer his wise words to researchers on how to manage during the COVID-19 pandemic.


Cell scientist to watch – Christine Faulkner

In an interview, Christine Faulkner talks about where her interest in plant science began, how she found the transition between Australia and the UK, and shares her thoughts on virtual conferences.


Read & Publish participation extends worldwide

“The clear advantages are rapid and efficient exposure and easy access to my article around the world. I believe it is great to have this publishing option in fast-growing fields in biomedical research.”

Dr Jaceques Behmoaras (Imperial College London) shares his experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 60 institutions in 12 countries taking part – find out more and view our full list of participating institutions.


JCS and COVID-19

For more information on measures Journal of Cell Science is taking to support the community during the COVID-19 pandemic, please see here.

If you have any questions or concerns, please do not hestiate to contact the Editorial Office.

Articles

  • Accepted manuscripts
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Special issues
  • Subject collections
  • Interviews
  • Sign up for alerts

About us

  • About Journal of Cell Science
  • Editors and Board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Journal Meetings
  • Workshops
  • The Company of Biologists

For Authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Fast-track manuscripts
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • JCS Prize
  • Manuscript transfer network
  • Biology Open transfer

Journal Info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contacts

  • Contact JCS
  • Subscriptions
  • Advertising
  • Feedback

Twitter   YouTube   LinkedIn

© 2021   The Company of Biologists Ltd   Registered Charity 277992