%0 Journal Article
%T The TSC22D, WNK, and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation.
%A Xiao YX
%A Lee SY
%A Aguilera-Uribe M
%A Samson R
%A Au A
%A Khanna Y
%A Liu Z
%A Cheng R
%A Aulakh K
%A Wei J
%A Farias AG
%A Reilly T
%A Birkadze S
%A Habsid A
%A Brown KR
%A Chan K
%A Mero P
%A Huang JQ
%A Billmann M
%A Rahman M
%A Myers C
%A Andrews BJ
%A Youn JY
%A Yip CM
%A Rotin D
%A Derry WB
%A Forman-Kay JD
%A Moses AM
%A Pritišanac I
%A Gingras AC
%A Moffat J
%J Cell Rep
%V 43
%N 7
%D 2024 Jul 23
%M 38980795
暂无%R 10.1016/j.celrep.2024.114417
%X 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.