1. Cell Biology
  2. Developmental Biology
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LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is a contributing factor in Townes-Brocks Syndrome

Research Article
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Cite this article as: eLife 2020;9:e55957 doi: 10.7554/eLife.55957

Abstract

Primary cilia are sensory organelles crucial for cell signaling during development and organ homeostasis. Cilia arise from centrosomes and their formation and function is governed by numerous factors. Through our studies on Townes-Brocks Syndrome (TBS), a rare disease linked to abnormal cilia formation in human fibroblasts, we uncovered the leucine-zipper protein LUZP1 as an interactor of truncated SALL1, a dominantly-acting protein causing the disease. Using TurboID proximity labeling and pulldowns, we show that LUZP1 associates with factors linked to centrosome and actin filaments. Here, we show that LUZP1 is a cilia regulator. It localizes around the centrioles and to actin cytoskeleton. Loss of LUZP1 reduces F-actin levels, facilitates ciliogenesis and alters Sonic Hedgehog signaling, pointing to a key role in cytoskeleton-cilia interdependency. Truncated SALL1 increases the ubiquitin proteasome-mediated degradation of LUZP1. Together with other factors, alterations in LUZP1 may be contributing to TBS etiology.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Laura Bozal-Basterra

    Functional Genomics, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. María Gonzalez-Santamarta

    Functional Genomics, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Veronica Muratore

    Functional Genomics, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Aitor Bermejo-Arteagabeitia

    Functional Genomics, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Carolina Da Fonseca

    Functional Genomics, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Orhi Barroso-Gomila

    Functional Genomics, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Mikel Azkargorta

    Proteomics Platform, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9115-3202
  8. Ibon Iloro

    Proteomics Platform, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Olatz Pampliega

    Department of Neurosciences, Achucarro Basque Center for Neuros, Leioa, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7924-6374
  10. Ricardo Andrade

    Analytical & High Resolution Biomedical Microscopy Core Facility, University of the Basque Country (UPV/EHU), Leioa, Spain
    Competing interests
    The authors declare that no competing interests exist.
  11. Natalia Martín-Martín

    Proteomics Unit, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  12. Tess C Branon

    Department of Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Alice Y Ting

    Department of Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8277-5226
  14. Jose A Rodríguez

    Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain
    Competing interests
    The authors declare that no competing interests exist.
  15. Arkaitz Carracedo

    Proteomics Unit, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  16. Felix Elortza

    Proteomics Platform, CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  17. James D Sutherland

    Functional Genomics, CIC bioGUNE, Derio, Spain
    For correspondence
    jsutherland@cicbiogune.es
    Competing interests
    The authors declare that no competing interests exist.
  18. Rosa Barrio

    Functional Genomics, CIC bioGUNE, Derio, Spain
    For correspondence
    rbarrio@cicbiogune.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9663-0669

Funding

Ministerio de Economía y Competitividad (BFU2017-84653-P)

  • Rosa Barrio

Asociacion Espanola Contra el Cancer (IDEAS175CARR)

  • Arkaitz Carracedo

Asociacion Espanola Contra el Cancer (GCTRA18006CARR)

  • Arkaitz Carracedo

La Caixa Foundation (HR17-00094)

  • Arkaitz Carracedo

European Commission (336343)

  • Arkaitz Carracedo

European Commission (PoC 754627)

  • Arkaitz Carracedo

European Commission (819242)

  • Arkaitz Carracedo

Ministerio de Economía y Competitividad (SEV-2016-0644)

  • Arkaitz Carracedo
  • Felix Elortza
  • James D Sutherland
  • Rosa Barrio

Ministerio de Economía y Competitividad (SAF2017-90900-REDT)

  • Rosa Barrio

European Commission (765445-EU)

  • Orhi Barroso-Gomila
  • James D Sutherland
  • Rosa Barrio

Basque Government (IT634-13)

  • Arkaitz Carracedo

Asociacion Espanola Contra el Cancer (POSTD19048BOZA)

  • Arkaitz Carracedo

Instituto de Salud Carlos III (PT13/0001/0027)

  • Arkaitz Carracedo

Basque Government (IKERTALDE IT1106-16)

  • Arkaitz Carracedo

Ministerio de Ciencia, Investigacion y Universidades (SAF2016-79381-R)

  • Arkaitz Carracedo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The use of human samples in this study was approved by the institutional review board (Ethics Committee at CIC bioGUNE) and appropriate informed consent was obtained from human subjects or their parents. protocol P-CBG-CBBA-2111)

Reviewing Editor

  1. Lotte Pedersen, University of Copenhagen, Denmark

Publication history

  1. Received: February 12, 2020
  2. Accepted: June 18, 2020
  3. Accepted Manuscript published: June 18, 2020 (version 1)
  4. Version of Record published: July 15, 2020 (version 2)

Copyright

© 2020, Bozal-Basterra 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.

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