LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is a contributing factor in Townes-Brocks Syndrome
- CIC bioGUNE, Spain
- Achucarro Basque Center for Neuros, Spain
- University of the Basque Country (UPV/EHU), Spain
- Stanford University, United States
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
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)
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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LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is a contributing factor in Townes-Brocks Syndrome
eLife 9:e55957.
https://doi.org/10.7554/eLife.55957
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