title: The Salih ataxia mutation impairs Rubicon endosomal localization.
abstract: We previously described a new form of recessive ataxia, Salih ataxia, in a large consanguineous Saudi Arabian family with three affected children carrying a new identified mutation in the KIAA0226 gene (c.2624delC; p.Ala875ValfsX146) coding for Rubicon. The pathogenicity of such mutation remains to be identified. Hence, we address the cellular impact of Rubicon p.Ala875ValfsX146 on endosomal/lysosomal machinery on cultured cells. We confirm that Rubicon colocalizes with the late endosome marker Rab7 and demonstrate that it also colocalizes with LampI at lysosomes. The Salih ataxia mutation leads to a diffuse cytosolic distribution and mislocalized protein from the late endosomes, indicating that deletion of the diacylglycerol binding-like motif in the mutant protein interferes with normal Rubicon subcellular localization and confirming the pathogenicity of the mutation.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université de Strasbourg, et Collège de France, 67404, Illkirch, France, mirna.assoum@univ-amu.fr.
authors.forename: M
authors.initials: M
authors.lastname: Assoum
authors.forename: M A
authors.initials: MA
authors.lastname: Salih
authors.forename: N
authors.initials: N
authors.lastname: Drouot
authors.forename: K
authors.initials: K
authors.lastname: Hnia
authors.forename: A
authors.initials: A
authors.lastname: Martelli
authors.forename: M
authors.initials: M
authors.lastname: Koenig
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004075:Diglycerides / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D012867:Skin / Q000166:cytology; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D000071183:Autophagy-Related Proteins; D004075:Diglycerides; D047908:Intracellular Signaling Peptides and Proteins; D052118:Lysosomal-Associated Membrane Protein 1; C552537:RUBCN protein, human; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins