Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Newest Articles
    • Current Issue
    • Methods & Resources
    • Archive
    • Subjects
  • Collections
  • Submit
    • Submit a Manuscript
    • Author Guidelines
    • License, Copyright, Fee
    • FAQ
    • Why Submit
  • About
    • About Us
    • Editors & Staff
    • Board Members
    • Licensing and Reuse
    • Reviewer Guidelines
    • Privacy Policy
    • Advertise
    • Contact Us
    • LSA LLC
  • Alerts
  • Other Publications
    • EMBO Press
    • The EMBO Journal
    • EMBO reports
    • EMBO Molecular Medicine
    • Molecular Systems Biology
    • Rockefeller University Press
    • Journal of Cell Biology
    • Journal of Experimental Medicine
    • Journal of General Physiology
    • Cold Spring Harbor Laboratory Press
    • Genes & Development
    • Genome Research

User menu

  • My alerts

Search

  • Advanced search
Life Science Alliance
  • Other Publications
    • EMBO Press
    • The EMBO Journal
    • EMBO reports
    • EMBO Molecular Medicine
    • Molecular Systems Biology
    • Rockefeller University Press
    • Journal of Cell Biology
    • Journal of Experimental Medicine
    • Journal of General Physiology
    • Cold Spring Harbor Laboratory Press
    • Genes & Development
    • Genome Research
  • My alerts
Life Science Alliance

Advanced Search

  • Home
  • Articles
    • Newest Articles
    • Current Issue
    • Methods & Resources
    • Archive
    • Subjects
  • Collections
  • Submit
    • Submit a Manuscript
    • Author Guidelines
    • License, Copyright, Fee
    • FAQ
    • Why Submit
  • About
    • About Us
    • Editors & Staff
    • Board Members
    • Licensing and Reuse
    • Reviewer Guidelines
    • Privacy Policy
    • Advertise
    • Contact Us
    • LSA LLC
  • Alerts
  • Follow lsa Template on Twitter
Research Article
Transparent Process
Open Access

Essential role of the Crk family-dosage in DiGeorge-like anomaly and metabolic homeostasis

View ORCID ProfileAkira Imamoto  Correspondence email, Sewon Ki, Leiming Li, Kazunari Iwamoto, Venkat Maruthamuthu, View ORCID ProfileJohn Devany, View ORCID ProfileOcean Lu, Tomomi Kanazawa, Suxiang Zhang, Takuji Yamada, Akiyoshi Hirayama, Shinji Fukuda, Yutaka Suzuki, View ORCID ProfileMariko Okada  Correspondence email
Akira Imamoto
1The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Akira Imamoto
  • For correspondence: aimamoto@uchicago.edu
Sewon Ki
2RIKEN Integrative Medical Sciences, Tsurumi, Yokohama, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leiming Li
1The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazunari Iwamoto
3Institute for Protein Research, Osaka University, Suita, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Venkat Maruthamuthu
4Department of Mechanical and Aerospace Engineering, Old Dominion University, Norfolk, VA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John Devany
5Department of Physics, The University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for John Devany
Ocean Lu
1The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ocean Lu
Tomomi Kanazawa
3Institute for Protein Research, Osaka University, Suita, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Suxiang Zhang
3Institute for Protein Research, Osaka University, Suita, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takuji Yamada
6Department of Life Science and Technology, Tokyo Institute of Technology, Meguro, Tokyo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akiyoshi Hirayama
7Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shinji Fukuda
7Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
8Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Kanagawa, Japan
9Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan
10PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yutaka Suzuki
11Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mariko Okada
2RIKEN Integrative Medical Sciences, Tsurumi, Yokohama, Kanagawa, Japan
3Institute for Protein Research, Osaka University, Suita, Osaka, Japan
12Center for Drug Design and Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mariko Okada
  • For correspondence: mokada@protein.osaka-u.ac.jp
Published 10 February 2020. DOI: 10.26508/lsa.201900635
  • Article
  • Figures & Data
  • Info
  • Metrics
  • Reviewer Comments
  • PDF
Loading

Abstract

CRK and CRKL (CRK-like) encode adapter proteins with similar biochemical properties. Here, we show that a 50% reduction of the family-combined dosage generates developmental defects, including aspects of DiGeorge/del22q11 syndrome in mice. Like the mouse homologs of two 22q11.21 genes CRKL and TBX1, Crk and Tbx1 also genetically interact, thus suggesting that pathways shared by the three genes participate in organogenesis affected in the syndrome. We also show that Crk and Crkl are required during mesoderm development, and Crk/Crkl deficiency results in small cell size and abnormal mesenchyme behavior in primary embryonic fibroblasts. Our systems-wide analyses reveal impaired glycolysis, associated with low Hif1a protein levels as well as reduced histone H3K27 acetylation in several key glycolysis genes. Furthermore, Crk/Crkl deficiency sensitizes MEFs to 2-deoxy-D-glucose, a competitive inhibitor of glycolysis, to induce cell blebbing. Activated Rapgef1, a Crk/Crkl-downstream effector, rescues several aspects of the cell phenotype, including proliferation, cell size, focal adhesions, and phosphorylation of p70 S6k1 and ribosomal protein S6. Our investigations demonstrate that Crk/Crkl-shared pathways orchestrate metabolic homeostasis and cell behavior through widespread epigenetic controls.

  • Received December 23, 2019.
  • Revision received January 20, 2020.
  • Accepted January 21, 2020.
  • © 2020 Imamoto et al.
Creative Commons logoCreative Commons logohttps://creativecommons.org/licenses/by/4.0/

This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

View Full Text
PreviousNext
Back to top
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Life Science Alliance.

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.
Essential role of the Crk family-dosage in DiGeorge-like anomaly and metabolic homeostasis
(Your Name) has sent you a message from Life Science Alliance
(Your Name) thought you would like to see the Life Science Alliance web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
The CRK family controls glucose metabolism and cell size
Akira Imamoto, Sewon Ki, Leiming Li, Kazunari Iwamoto, Venkat Maruthamuthu, John Devany, Ocean Lu, Tomomi Kanazawa, Suxiang Zhang, Takuji Yamada, Akiyoshi Hirayama, Shinji Fukuda, Yutaka Suzuki, Mariko Okada
Life Science Alliance Feb 2020, 3 (2) e201900635; DOI: 10.26508/lsa.201900635

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
The CRK family controls glucose metabolism and cell size
Akira Imamoto, Sewon Ki, Leiming Li, Kazunari Iwamoto, Venkat Maruthamuthu, John Devany, Ocean Lu, Tomomi Kanazawa, Suxiang Zhang, Takuji Yamada, Akiyoshi Hirayama, Shinji Fukuda, Yutaka Suzuki, Mariko Okada
Life Science Alliance Feb 2020, 3 (2) e201900635; DOI: 10.26508/lsa.201900635
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
Issue Cover

In this Issue

Volume 3, No. 2
February 2020
  • Table of Contents
  • Cover (PDF)
  • About the Cover
  • Masthead (PDF)
Advertisement

Jump to section

  • Article
    • Abstract
    • Introduction
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgements
    • References
  • Figures & Data
  • Info
  • Metrics
  • Reviewer Comments
  • PDF

Subjects

  • Cell Biology
  • Genetics, Gene Therapy & Genetic Disease
  • Metabolism

Related Articles

  • No related articles found.

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • SorCS1 in amyloid-β synaptic pathology
  • The GET pathway acts in promoting mitophagy
  • Proximity to the SC promotes exchanges
Show more Research Article

Similar Articles

EMBO Press LogoRockefeller University Press LogoCold Spring Harbor Logo

Content

  • Home
  • Newest Articles
  • Current Issue
  • Archive
  • Subject Collections

For Authors

  • Submit a Manuscript
  • Author Guidelines
  • License, copyright, Fee

Other Services

  • Alerts
  • Twitter
  • RSS Feeds

More Information

  • Editors & Staff
  • Reviewer Guidelines
  • Feedback
  • Licensing and Reuse
  • Privacy Policy

ISSN: 2575-1077
© 2023 Life Science Alliance LLC

Life Science Alliance is registered as a trademark in the U.S. Patent and Trade Mark Office and in the European Union Intellectual Property Office.