title: Human FAM154A (SAXO1) is a microtubule-stabilizing protein specific to cilia and related structures.
abstract: Cilia and flagella are microtubule-based organelles present at the surface of most cells, ranging from protozoa to vertebrates, in which these structures are implicated in processes from morphogenesis to cell motility. In vertebrate neurons, microtubule-associated MAP6 proteins stabilize cold-resistant microtubules through their Mn and Mc modules, and play a role in synaptic plasticity. Although centrioles, cilia and flagella have cold-stable microtubules, MAP6 proteins have not been identified in these organelles, suggesting that additional proteins support this role in these structures. Here, we characterize human FAM154A (hereafter referred to as hSAXO1) as the first human member of a widely conserved family of MAP6-related proteins specific to centrioles and cilium microtubules. Our data demonstrate that hSAXO1 binds specifically to centriole and cilium microtubules. We identify, in vivo and in vitro, hSAXO1 Mn modules as responsible for microtubule binding and stabilization as well as being necessary for ciliary localization. Finally, overexpression and knockdown studies show that hSAXO1 modulates axoneme length. Taken together, our findings suggest a fine regulation of hSAXO1 localization and important roles in cilium biogenesis and function.
authors: University Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France Institut Polytechnique de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France.
authors: Denis
authors: D
authors: Dacheux
authors: University Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France.
authors: Benoit
authors: B
authors: Roger
authors: INSERM, Centre de Recherche U836, F-38000, Grenoble, France University Grenoble Alpes, Grenoble Institut des Neurosciences, F-38000, Grenoble, France.
authors: Christophe
authors: C
authors: Bosc
authors: University Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France.
authors: Nicolas
authors: N
authors: Landrein
authors: University Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France.
authors: Emmanuel
authors: E
authors: Roche
authors: CHU de Bordeaux, Centre Aliénor d'Aquitaine, Laboratoire de Biologie de la Reproduction, F-33000 Bordeaux, France.
authors: Lucie
authors: L
authors: Chansel
authors: University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, F-33000 Bordeaux, France INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, F-33000 Bordeaux, France.
authors: Thomas
authors: T
authors: Trian
authors: INSERM, Centre de Recherche U836, F-38000, Grenoble, France University Grenoble Alpes, Grenoble Institut des Neurosciences, F-38000, Grenoble, France CEA, Institut de Recherches en Technologies et Sciences pour le Vivant, GPC, F-38000 Grenoble, France.
authors: Annie
authors: A
authors: Andrieux
authors: CHU de Bordeaux, Centre Aliénor d'Aquitaine, Laboratoire de Biologie de la Reproduction, F-33000 Bordeaux, France.
authors: Aline
authors: A
authors: Papaxanthos-Roche
authors: University Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, F-33000 Bordeaux, France INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, F-33000 Bordeaux, France.
authors: Roger
authors: R
authors: Marthan
authors: University Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France.
authors: Derrick R
authors: DR
authors: Robinson
authors: University Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France melanie.bonhivers@u-bordeaux.fr.
authors: Mélanie
authors: M
authors: Bonhivers
mesh_terms: D054468:Axoneme / Q000235:genetics / Q000378:metabolism; D002502:Centrioles / Q000235:genetics / Q000378:metabolism; D002923:Cilia / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; C552553:FAM161A protein, human; C491894:MAP6 protein, human; D008869:Microtubule-Associated Proteins
keywords: Axoneme; Basal body; Centriole; Cilium; Cytoskeleton; Epithelial cell; Flagellum; MAP6; Microtubule; Microtubule-stabilizing protein; Spermatozoon