C9orf72, a protein associated with amyotrophic lateral sclerosis (ALS) is a guanine nucleotide exchange factor

PeerJ

article

Shalini Iyer¹  Vasanta Subramanian¹  K. Ravi Acharya¹ 

[1] Department of Biology and Biochemistry, University of Bath

关键词: C9orf72;    Guanine nucleotide exchange factor;    Protein expression;    Protein purification;    Size-exclusion chromatography;    Rab GTPases;    ALS;    Neurodegeneration;   

DOI  :  10.7717/peerj.5815

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two late onset neurodegenerative diseases, have been shown to share overlapping cellular pathologies and genetic origins. Studies suggest that a hexanucleotide repeat expansion in the first intron of the C9orf72 gene is the most common cause of familial FTD and ALS pathology. The C9orf72 protein is predicted to be a differentially expressed in normal and neoplastic cells domain protein implying that C9orf72 functions as a guanine nucleotide exchange factor (GEF) to regulate specific Rab GTPases. Reported studies thus far point to a putative role for C9orf72 in lysosome biogenesis, vesicular trafficking, autophagy and mechanistic target of rapamycin complex1 (mTORC1) signaling. Here we report the expression, purification and biochemical characterization of C9orf72 protein. We conclusively show that C9orf72 is a GEF. The distinctive presence of both Rab- and Rho-GTPase GEF activities suggests that C9orf72 may function as a dual exchange factor coupling physiological functions such as cytoskeleton modulation and autophagy with endocytosis.

【 授权许可】

CC BY