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Published on: April 4, 2018
The Salih ataxia mutation impairs Rubicon endosomal localization
M Assoum1, M A Salih, N Drouot
1Institut 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.
Cerebellum (London, England)
|June 4, 2013
Summary
Salih ataxia, a rare genetic disorder, is caused by a mutation in the KIAA0226 gene (Rubicon). This study reveals the mutation disrupts Rubicon
Area of Science:
- Genetics
- Cell Biology
- Neuroscience
Background:
- Salih ataxia is a newly identified form of recessive ataxia.
- A specific mutation (c.2624delC; p.Ala875ValfsX146) in the KIAA0226 gene, encoding Rubicon, was identified in affected individuals.
- The pathogenicity of this mutation requires elucidation.
Purpose of the Study:
- To investigate the cellular impact of the Rubicon p.Ala875ValfsX146 mutation.
- To analyze the effect on the endosomal/lysosomal machinery in cultured cells.
Main Methods:
- Utilized cultured cells to study the Rubicon p.Ala875ValfsX146 mutation.
- Confirmed Rubicon colocalization with the late endosome marker Rab7.
- Demonstrated Rubicon colocalization with the lysosome marker LampI.
Main Results:
- The Salih ataxia mutation results in a diffuse cytosolic distribution of Rubicon.
- The mutant Rubicon protein is mislocalized from late endosomes.
- Deletion of the diacylglycerol binding-like motif impairs Rubicon's subcellular localization.
Conclusions:
- The identified KIAA0226 mutation is pathogenic.
- The mutation disrupts Rubicon's normal localization within the endosomal/lysosomal pathway.
- This mislocalization provides insight into the cellular mechanisms underlying Salih ataxia.
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