MPDH forms the cytoophidium in zebrafis

Autor(es)

Keppeke, Gerson Dierley ^{[1, 2]} ; Chang, Chia-Chun ^[1] ; Antos, Christopher L. ^[1] ; Peng, Min ^[3] ; Sung, Li-Ying ^{[3, 4]} ; Andrade, Luis Eduardo Coelho ^[2] ; Liu, Ji-Long ^[1]

Afiliação do(s) autor(es)

^[1] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210 - Peoples R China

^[2] Univ Fed Sao Paulo, Div Rheumatol, Escola Paulista Med, BR-04023062 Sao Paulo, SP - Brazil

^[3] Natl Taiwan Univ, Inst Biotechnol, Taipei 106 - Taiwan

^[4] Acad Sinica, Agr Biotechnol Res Ctr, Taipei 115 - Taiwan

• Tipo de documento: Artigo Científico
• Fonte: Developmental Biology; v. 478, p. 89-101, OCT 2021.
• Citações Web of Science: 1

Resumo

Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in de novo guanine nucleotide biosynthesis. Its activity is negatively regulated by the binding of GTP. IMPDH can form a membraneless subcellular structure termed the cytoophidium in response to certain changes in the metabolic status of the cell. The polymeric form of IMPDH, which is the subunit of the cytoophidium, has been shown to be more resistant to the inhibition by GTP at physiological concentrations, implying a functional correlation between cytoophidium formation and the upregulation of GTP biosynthesis. Herein we demonstrate that zebrafish IMPDH1b and IMPDH2 isoforms can assemble abundant cytoophidium in most of cultured cells under stimuli, while zebrafish IMPDH1a shows distinctive properties of forming the cytoophidium in different cell types. Point mutations that disrupt cytoophidium structure in mammalian models also prevent the aggregation of zebrafish IMPDHs. In addition, we discover the presence of the IMPDH cytoophidium in various tissues of larval and adult fish under normal growth conditions. Our results reveal that polymerization and cytoophidium assembly of IMPDH can be a regulatory machinery conserved among vertebrates, and with specific physiological purposes. (AU)

• Processo FAPESP: 17/20745-1 - Depleção de autoanticorpos por edição gênica com o sistema CRISPR/Cas9 em plasmócitos autorreativos
• Beneficiário: Gerson Dierley Keppeke
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores