The Cerebellum

, Volume 12, Issue 6, pp 835–840 | Cite as

The Salih Ataxia Mutation Impairs Rubicon Endosomal Localization

  • M. Assoum
  • M. A. Salih
  • N. Drouot
  • K. Hnia
  • A. Martelli
  • M. Koenig
Research Article


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.


Salih ataxia Rubicon Rab7 DAG binding-like motif 



We are indebted to S. Schmucker, H. Puccio, and JL Mandel for support and fruitful discussions. We wish to thank L. Reutenauer for advice and technical help. This study was supported by funds from the Institut National de la Santé et de la Recherche Médicale (INSERM), the Center National de la Recherche Scientifique (CNRS), and the Agence Nationale pour la Recherche-Maladies Rares and Maladies Neurologiques et Psychiatriques (ANR-09-MNPS-001-01 to M.K.). M.A. was supported by a fellowship from the Association Française contre les Myopathies (AFM). M.A.S. was supported by CMRC (project no. 05-495), College of Medicine, King Saud University, Riyadh, Saudi Arabia. The scientific and technical assistance of the IGBMC facilities (imaging facilities, peptide synthesis, and cell culture) was highly appreciated.

Conflict of Interest

The authors declare no conflict of interest in the work presented in this manuscript.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • M. Assoum
    • 1
    • 3
  • M. A. Salih
    • 2
  • N. Drouot
    • 1
  • K. Hnia
    • 1
  • A. Martelli
    • 1
  • M. Koenig
    • 1
  1. 1.Institut de Génétique et de Biologie Moléculaire et CellulaireCNRS/INSERM/Université de Strasbourg, et Collège de FranceIllkirchFrance
  2. 2.Division of Pediatric Neurology, College of MedicineKing Saud UniversityRiyadhSaudi Arabia
  3. 3.Laboratoire de Génétique Médicale et de Génomique FonctionnelleFaculté de Médecine de la TimoneMarseille cedexFrance

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