Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Xiao, YX; Lee, SY; Aguilera-Uribe, M; Samson, R; Au, A; Khanna, Y; Liu, Z; Cheng, R; Aulakh, K; Wei, J; Farias, AG; Reilly, T; Birkadze, S; Habsid, A; Brown, KR; Chan, K; Mero, P; Huang, JQ; Billmann, M; Rahman, M; Myers, C; Andrews, BJ; Youn, JY; Yip, CM; Rotin, D; Derry, WB; Forman-Kay, JD; Moses, AM; Pritišanac, I; Gingras, AC; Moffat, J.
The TSC22D, WNK, and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation.
Cell Rep. 2024; 43(7):114417 Doi: 10.1016/j.celrep.2024.114417
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Khanna Yukti; Pritisanac Iva
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Abstract:: The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis to identify an unappreciated relationship between TSC22D2, WNK1, and NRBP1 in regulating cell volume homeostasis. All of these genes have paralogs and are functionally buffered for osmo-sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK, and NRBP family members physically associate into biomolecular condensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans revealed that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is accompanied by rapid IDR length expansion in WNK-family kinases. Our study reveals that TSC22D, WNK, and NRBP genes evolved in metazoans to co-regulate rapid cell volume changes in response to osmolarity.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; Animals - administration & dosage; Cell Size - administration & dosage; WNK Lysine-Deficient Protein Kinase 1 - metabolism, genetics; Evolution, Molecular - administration & dosage; HEK293 Cells - administration & dosage; Protein Binding - administration & dosage; Multigene Family - administration & dosage; Osmotic Pressure - administration & dosage