Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; ProteoRed-ISCIII, Instituto de Salud Carlos III, Madrid, Spain
Ibon Iloro
Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; ProteoRed-ISCIII, Instituto de Salud Carlos III, Madrid, Spain
Department of Neurosciences, University of the Basque Country, Achucarro Basque Center for Neuroscience-UPV/EHU, Leioa, Spain
Ricardo Andrade
Analytical & High Resolution Biomedical Microscopy Core Facility, University of the Basque Country (UPV/EHU), Leioa, Spain
Natalia Martín-Martín
Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain
Tess C Branon
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, United States; Departments of Genetics, Chemistry and Biology, Stanford University, Stanford, United States
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, United States; Departments of Genetics, Chemistry and Biology, Stanford University, Stanford, United States; Chan Zuckerberg Biohub, San Francisco, United States
Jose A Rodríguez
Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain
Arkaitz Carracedo
Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain; Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bilbao, Spain
Felix Elortza
Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; ProteoRed-ISCIII, Instituto de Salud Carlos III, Madrid, Spain
James D Sutherland
Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain
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.
