Journal article

C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking

Manal A Farg, Vinod Sundaramoorthy, Jessica M Sultana, Shu Yang, Rachel AK Atkinson, Vita Levina, Mark A Halloran, Paul A Gleeson, Ian P Blair, Kai Y Soo, Anna E King, Julie D Atkin



Intronic expansion of a hexanucleotide GGGGCC repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene is the major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. However, the cellular function of the C9ORF72 protein remains unknown. Here, we demonstrate that C9ORF72 regulates endosomal trafficking. C9ORF72 colocalized with Rab proteins implicated in autophagy and endocytic transport: Rab1, Rab5, Rab7 and Rab11 in neuronal cell lines, primary cortical neurons and human spinal cord motor neurons, consistent with previous predictions that C9ORF72 bears Rab guanine exchange factor activity. Consistent with this notion, C9ORF72 was present in the extrac..

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University of Melbourne Researchers


Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported by funding from National Health and Medical Research Council of Australia (project grants 1006141, 1004670 and 1030513), MND Research Institute of Australia and Bethlehem Griffiths Research Council. Funding to pay the Open Access publication charges for this article was provided by LaTrobe University.