Cell Reports (Jul 2024)
The TSC22D, WNK, and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation
- Yu-Xi Xiao,
- Seon Yong Lee,
- Magali Aguilera-Uribe,
- Reuben Samson,
- Aaron Au,
- Yukti Khanna,
- Zetao Liu,
- Ran Cheng,
- Kamaldeep Aulakh,
- Jiarun Wei,
- Adrian Granda Farias,
- Taylor Reilly,
- Saba Birkadze,
- Andrea Habsid,
- Kevin R. Brown,
- Katherine Chan,
- Patricia Mero,
- Jie Qi Huang,
- Maximilian Billmann,
- Mahfuzur Rahman,
- Chad Myers,
- Brenda J. Andrews,
- Ji-Young Youn,
- Christopher M. Yip,
- Daniela Rotin,
- W. Brent Derry,
- Julie D. Forman-Kay,
- Alan M. Moses,
- Iva Pritišanac,
- Anne-Claude Gingras,
- Jason Moffat
Affiliations
- Yu-Xi Xiao
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- Seon Yong Lee
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Magali Aguilera-Uribe
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- Reuben Samson
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada
- Aaron Au
- Institute for Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada
- Yukti Khanna
- Otto-Loewi Research Center, Division of Medicinal Chemistry, Medical University of Graz, Neue Stiftingtalstrabe 6, 8010, Graz, Austria
- Zetao Liu
- Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada
- Ran Cheng
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Kamaldeep Aulakh
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Jiarun Wei
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Adrian Granda Farias
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- Taylor Reilly
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- Saba Birkadze
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- Andrea Habsid
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Kevin R. Brown
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Katherine Chan
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Patricia Mero
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Jie Qi Huang
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada
- Maximilian Billmann
- Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, 53127 Bonn, Germany
- Mahfuzur Rahman
- Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA
- Chad Myers
- Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA
- Brenda J. Andrews
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada
- Ji-Young Youn
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada
- Christopher M. Yip
- Institute for Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada
- Daniela Rotin
- Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada
- W. Brent Derry
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Julie D. Forman-Kay
- Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada
- Alan M. Moses
- Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada
- Iva Pritišanac
- Otto-Loewi Research Center, Division of Medicinal Chemistry, Medical University of Graz, Neue Stiftingtalstrabe 6, 8010, Graz, Austria
- Anne-Claude Gingras
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada
- Jason Moffat
- Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Institute for Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Corresponding author
- Journal volume & issue
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Vol. 43,
no. 7
p. 114417
Abstract
Summary: 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.
