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TSC22D, WNK and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation

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. Each 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269526 | GEO | 2024/11/15

REPOSITORIES: GEO

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TSC22D, WNK and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation

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