{Reference Type}: Journal Article
{Title}: The TSC22D, WNK, and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation.
{Author}: 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;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 7
{Year}: 2024 Jul 23
暂无{DOI}: 10.1016/j.celrep.2024.114417
{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.