1. Cell Biology
  2. Developmental Biology
Download icon

LINKIN, a new transmembrane protein necessary for cell adhesion

  1. Mihoko Kato
  2. Tsui-Fen Chou
  3. Collin Z Yu
  4. John A DeModena
  5. Paul W Sternberg  Is a corresponding author
  1. Howard Hughes Medical Institute, California Institute of Technology, United States
  2. University of California, San Francisco, United States
Research Article
  • Cited 8
  • Views 2,073
  • Annotations
Cite this article as: eLife 2014;3:e04449 doi: 10.7554/eLife.04449

Abstract

In epithelial collective migration, leader and follower cells migrate while maintaining cell-cell adhesion and tissue polarity. We have identified a conserved protein and interactors required for maintaining cell adhesion during a simple collective migration in the developing C. elegans male gonad. LINKIN is a previously uncharacterized, transmembrane protein conserved throughout Metazoa. We identified seven atypical FG-GAP domains in the extracellular domain, which potentially folds into a β-propeller structure resembling the α-integrin ligand-binding domain. C. elegans LNKN-1 localizes to the plasma membrane of all gonadal cells, with apical and lateral bias. We identified the LINKIN interactors RUVBL1, RUVBL2, and α-tubulin by using SILAC mass spectrometry on human HEK 293T cells and testing candidates for lnkn-1-like function in C. elegans male gonad. We propose that LINKIN promotes adhesion between neighboring cells through its extracellular domain and regulates microtubule dynamics through RUVBL proteins at its intracellular domain.

Article and author information

Author details

  1. Mihoko Kato

    Division of Biology and BIological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Tsui-Fen Chou

    Division of Biology and BIological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Collin Z Yu

    School of Pharmacy, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. John A DeModena

    Division of Biology and BIological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Paul W Sternberg

    Division of Biology and BIological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States
    For correspondence
    pws@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Janet Rossant, University of Toronto, Canada

Publication history

  1. Received: August 21, 2014
  2. Accepted: November 28, 2014
  3. Accepted Manuscript published: December 1, 2014 (version 1)
  4. Version of Record published: December 24, 2014 (version 2)

Copyright

© 2014, Kato et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,073
    Page views
  • 216
    Downloads
  • 8
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Xiaoshan Shi et al.
    Research Article

    The selective autophagy pathways of xenophagy and mitophagy are initiated when the adaptor NDP52 recruits the ULK1 complex to autophagic cargo. Hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) was used to map the membrane and NDP52 binding sites of the ULK1 complex to unique regions of the coiled coil of the FIP200 subunit. Electron microscopy of the full-length ULK1 complex shows that the FIP200 coiled coil projects away from the crescent-shaped FIP200 N-terminal domain dimer. NDP52 allosterically stimulates membrane-binding by FIP200 and the ULK1 complex by promoting a more dynamic conformation of the membrane-binding portion of the FIP200 coiled coil. Giant unilamellar vesicle (GUV) reconstitution confirmed that membrane recruitment by the ULK1 complex is triggered by NDP52 engagement. These data reveal how the allosteric linkage between NDP52 and the ULK1 complex could drive the first membrane recruitment event of phagophore biogenesis in xenophagy and mitophagy.

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Tatsuhisa Tsuboi et al.
    Research Article

    Mitochondria are dynamic organelles that must precisely control their protein composition according to cellular energy demand. Although nuclear-encoded mRNAs can be localized to the mitochondrial surface, the importance of this localization is unclear. As yeast switch to respiratory metabolism, there is an increase in the fraction of the cytoplasm that is mitochondrial. Our data point to this change in mitochondrial volume fraction increasing the localization of certain nuclear-encoded mRNAs to the surface of the mitochondria. We show that mitochondrial mRNA localization is necessary and sufficient to increase protein production to levels required during respiratory growth. Furthermore, we find that ribosome stalling impacts mRNA sensitivity to mitochondrial volume fraction and counterintuitively leads to enhanced protein synthesis by increasing mRNA localization to mitochondria. This points to a mechanism by which cells are able to use translation elongation and the geometric constraints of the cell to fine-tune organelle-specific gene expression through mRNA localization.