title: Plant toxin β-ODAP activates integrin β1 and focal adhesion: A critical pathway to cause neurolathyrism.
abstract: Neurolathyrism is a unique neurodegeneration disease caused by β-N-oxalyl-L-α, β- diaminopropionic (β-ODAP) present in grass pea seed (Lathyrus stativus L.) and its pathogenetic mechanism is unclear. This issue has become a critical restriction to take full advantage of drought-tolerant grass pea as an elite germplasm resource under climate change. We found that, in a human glioma cell line, β-ODAP treatment decreased mitochondrial membrane potential, leading to outside release and overfall of Ca2+from mitochondria to cellular matrix. Increased Ca2+in cellular matrix activated the pathway of ECM, and brought about the overexpression of β1 integrin on cytomembrane surface and the phosphorylation of focal adhesion kinase (FAK). The formation of high concentration of FA units on the cell microfilaments further induced overexpression of paxillin, and then inhibited cytoskeleton polymerization. This phenomenon turned to cause serious cell microfilaments distortion and ultimately cytoskeleton collapse. We also conducted qRT-PCR verification on RNA-sequence data using 8 randomly chosen genes of pathway enrichment, and confirmed that the data was statistically reliable. For the first time, we proposed a relatively complete signal pathway to neurolathyrism. This work would help open a new window to cure neurolathyrism, and fully utilize grass pea germplasm resource under climate change.
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: Rui-Yue
authors.initials: RY
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.|Department of Orthopaedics Surgery, General Hospital of Chinese People's Armed Police Force, Beijing, 100039, China.
authors.forename: Geng-Yan
authors.initials: GY
authors.lastname: Xing
authors.affiliation: School of Radiation Medicine and Protection, Soochow University, Building 402 Room 2222, 199 Renai Road, Suzhou 215123, Jiangsu, China.
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: Feng-Min
authors.initials: FM
authors.lastname: Li
authors.affiliation: School of Radiation Medicine and Protection, Soochow University, Building 402 Room 2222, 199 Renai Road, Suzhou 215123, Jiangsu, China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Hu
authors.affiliation: Institute Plant Biotechnology for Developing Countries (IPBO), Department of Molecular Genetics, Faculty of Sciences, K.L. Ledeganckstraat 35, Ghent University, B-9000 Gent, Belgium.
authors.forename: Fernand
authors.initials: F
authors.lastname: Lambein
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: Jun-Lan
authors.initials: JL
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: Sheng-Xiang
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: Zhi-Xiao
authors.initials: ZX
authors.lastname: Li
authors.affiliation: State Key Laboratory of Grassland Agro-ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China.
authors.forename: You-Cai
authors.initials: YC
authors.lastname: Xiong
mesh_terms: D000599:Amino Acids, Diamino / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix; D022001:Focal Adhesions / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D007842:Lathyrism / Q000209:etiology / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D055503:Protein Multimerization; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects; D014118:Toxins, Biological / Q000494:pharmacology*; D059467:Transcriptome
chemical_list: D000599:Amino Acids, Diamino; D019012:Integrin beta1; D014118:Toxins, Biological; C100126:oxalyldiaminopropionic acid; D002118:Calcium