NOCA-1 Functions with γ-tubulin and in parallel to Patronin to assemble non-centrosomal microtubule arrays in C. elegans

  1. Shaohe Wang
  2. Di Wu
  3. Sophie Quintin
  4. Rebecca A Green
  5. Dhanya K Cheerambathur
  6. Stacy D Ochoa
  7. Arshad Desai
  8. Karen Oegema  Is a corresponding author
  1. University of California, San Diego, United States
  2. Université de Strasbourg, France

Abstract

Non-centrosomal microtubule arrays assemble in differentiated tissues to perform mechanical and transport-based functions. Here, we identify C. elegans NOCA-1 as a protein with homology to vertebrate ninein. NOCA-1 contributes to the assembly of non-centrosomal microtubule arrays in multiple tissues. In the larval epidermis, NOCA-1 functions redundantly with the minus end protection factor Patronin/PTRN-1 to assemble a circumferential microtubule array essential for worm growth and morphogenesis. Controlled degradation of a γ-tubulin complex subunit in this tissue revealed that γ-tubulin acts with NOCA-1 in parallel to Patronin/PTRN-1. In the germline, NOCA-1 and γ-tubulin co-localize at the cell surface, and inhibiting either leads to a microtubule assembly defect. γ-tubulin targets independently of NOCA-1, but NOCA-1 targeting requires γ-tubulin when a non-essential putatively palmitoylated cysteine is mutated. These results show that NOCA-1 acts with γ-tubulin to assemble non-centrosomal arrays in multiple tissues and highlight functional overlap between the ninein and Patronin protein families.

Article and author information

Author details

  1. Shaohe Wang

    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Di Wu

    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sophie Quintin

    Institut Génétique Biologie Moléculaire Ceasllulaire, Faculté de médecine, Université de Strasbourg, Strasbourg, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Rebecca A Green

    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dhanya K Cheerambathur

    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Stacy D Ochoa

    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Arshad Desai

    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Karen Oegema

    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
    For correspondence
    koegema@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: May 11, 2015
  2. Accepted: September 12, 2015
  3. Accepted Manuscript published: September 15, 2015 (version 1)
  4. Version of Record published: October 16, 2015 (version 2)

Copyright

© 2015, Wang 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

  • 3,402
    Page views
  • 907
    Downloads
  • 77
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, 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)

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

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

  1. Shaohe Wang
  2. Di Wu
  3. Sophie Quintin
  4. Rebecca A Green
  5. Dhanya K Cheerambathur
  6. Stacy D Ochoa
  7. Arshad Desai
  8. Karen Oegema
(2015)
NOCA-1 Functions with γ-tubulin and in parallel to Patronin to assemble non-centrosomal microtubule arrays in C. elegans
eLife 4:e08649.
https://doi.org/10.7554/eLife.08649
  1. Further reading

Further reading

    1. Cell Biology
    2. Genetics and Genomics
    Shawn P Shortill, Mia S Frier ... Elizabeth Conibear
    Research Article Updated

    Membrane trafficking pathways perform important roles in establishing and maintaining the endosomal network. Retrograde protein sorting from the endosome is promoted by conserved SNX-BAR-containing coat complexes including retromer which enrich cargo at tubular microdomains and generate transport carriers. In metazoans, retromer cooperates with VARP, a conserved VPS9-domain GEF, to direct an endosomal recycling pathway. The function of the yeast VARP homolog Vrl1 has been overlooked due to an inactivating mutation found in commonly studied strains. Here, we demonstrate that Vrl1 has features of a SNX-BAR coat protein and forms an obligate complex with Vin1, the paralog of the retromer SNX-BAR protein Vps5. Unique features in the Vin1 N-terminus allow Vrl1 to distinguish it from Vps5, thereby forming a complex that we have named VINE. The VINE complex occupies endosomal tubules and redistributes a conserved mannose 6-phosphate receptor-like protein from endosomes. We also find that membrane recruitment by Vin1 is essential for Vrl1 GEF activity, suggesting that VINE is a multifunctional coat complex that regulates trafficking and signaling events at the endosome.

    1. Cell Biology
    Jill T Kuwabara, Akitoshi Hara ... Michelle D Tallquist
    Research Article

    Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. Although fibrosis accompanies many cardiac pathologies and is generally deleterious, the role of fibroblasts in maintaining the basal ECM network and in fibrosis in vivo is poorly understood. We genetically ablated fibroblasts in mice to evaluate the impact on homeostasis of adult ECM and cardiac function after injury. Fibroblast-ablated mice demonstrated a substantive reduction in cardiac fibroblasts, but fibrillar collagen and the ECM proteome were not overtly altered when evaluated by quantitative mass spectrometry and N-terminomics. However, the distribution and quantity of collagen VI, a microfibrillar collagen that forms an open network with the basement membrane, was reduced. In fibroblast-ablated mice, cardiac function was better preserved following angiotensin II/phenylephrine (AngII/PE)-induced fibrosis and myocardial infarction (MI). Analysis of cardiomyocyte function demonstrated altered sarcomere shortening and slowed calcium decline in both uninjured and AngII/PE infused fibroblast-ablated mice. After MI, the residual resident fibroblasts responded to injury, albeit with reduced proliferation and numbers immediately after injury. These results indicate that the adult mouse heart tolerates a significant degree of fibroblast loss with potentially beneficial impact on cardiac function after injury. The cardioprotective effect of controlled fibroblast reduction may have therapeutic value in heart disease.