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LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is altered in Townes-Brocks Syndrome

By Laura Bozal-Basterra, María Gonzalez-Santamarta, Aitor Bermejo-Arteagabeitia, Carolina Da Fonseca, Olatz Pampliega, Ricardo Andrade, Natalia Martín-Martín, Tess C Branon, Alice Y. Ting, Arkaitz Carracedo, Jose A. Rodríguez, Felix Elortza, James D Sutherland, Rosa Barrio

Posted 31 Jul 2019
bioRxiv DOI: 10.1101/721316 (published DOI: 10.7554/eLife.55957)

Primary cilia are sensory organelles that are crucial for cell signaling during development and organ homeostasis. Cilia arise from the centrosome and their formation is governed by numerous regulatory factors. We show that the leucine-zipper protein LUZP1 localizes to the pericentriolar material and actin cytoskeleton. Using TurboID proximity labeling and pulldowns, LUZP1 associates with factors linked to centrosome and actin filaments. Loss of LUZP1 reduces F-actin levels, facilitating ciliogenesis and altering Sonic Hedgehog signaling, pointing to a key role in the cytoskeleton-cilia interdependency. Moreover, we show that LUZP1 interacts with a truncated form of the transcription factor SALL1 that causes Townes-Brocks Syndrome. TBS is characterized by digit, heart and kidney malformations and is linked in part to defective cilia. Truncated SALL1 increases the ubiquitin proteasome-mediated degradation of LUZP1. Alteration of LUZP1 levels may be a contributing factor to TBS, suggesting possible therapies using modulators of cilia and cytoskeletal function.

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