title: First evidence of pathogenicity of V234I mutation of hVAPB found in Amyotrophic Lateral Sclerosis.
abstract: Amyotrophic Lateral Sclerosis is a motor neurodegenerative disease which is characterized by progressive loss of motor neurons followed by paralysis and eventually death. In human, VAMP-associated protein B (VAPB) is the causative gene of the familial form of ALS8. Previous studies have shown that P56S and T46I point mutations of hVAPB are present in this form of ALS. Recently, another mutation, V234I of hVAPB was found in one familial case of ALS. This is the first study where we have shown that V234I-VAPB does not form aggregate like other two mutants of VAPB and localizes differently than the wild type VAPB. It induces Ubiquitin aggregation followed by cell death. We propose that V234I-VAPB exhibits the characteristics of ALS in spite of not having the typical aggregation property of different mutations in various neurodegenerative diseases.
authors.affiliation: Department of Biochemistry, University of Calcutta, India.
authors.forename: Dhrubajyoti
authors.initials: D
authors.lastname: Chattopadhyay
authors.affiliation: Department of Biochemistry, University of Calcutta, India. Electronic address: ssshriya448@gmail.com.
authors.forename: Soma
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D002470:Cell Survival; D059865:Endoplasmic Reticulum Stress; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000235:genetics*; D009154:Mutation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D056811:Unfolded Protein Response
chemical_list: C496750:KCNIP1 protein, human; D051605:Kv Channel-Interacting Proteins
keywords: ALS; Cell viability; Cross-linking; Pathogenicity; Ubiquitination