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

CP: Molecular biology NRBP pseudo-kinases TSC22D family WNK kinases biomolecular condensates cell volume control essential genes genetic buffering genetic interactions intrinsic disordered regions paralog dominance

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
08 Jul 2024
Historique:
received: 22 02 2024
revised: 08 05 2024
accepted: 13 06 2024
medline: 9 7 2024
pubmed: 9 7 2024
entrez: 9 7 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2024.114417 PMID: 38980795
pubmed: 38980795
pii: S2211-1247(24)00746-0
doi: 10.1016/j.celrep.2024.114417
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114417

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Yu-Xi Xiao (YX)

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 (SY)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Magali Aguilera-Uribe (M)

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 (R)

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 (A)

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 (Y)

Otto-Loewi Research Center, Division of Medicinal Chemistry, Medical University of Graz, Neue Stiftingtalstrabe 6, 8010, Graz, Austria.

Zetao Liu (Z)

Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

Ran Cheng (R)

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 (K)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Jiarun Wei (J)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Adrian Granda Farias (AG)

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 (T)

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 (S)

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 (A)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Kevin R Brown (KR)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Katherine Chan (K)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Patricia Mero (P)

Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Jie Qi Huang (JQ)

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

Maximilian Billmann (M)

Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.

Mahfuzur Rahman (M)

Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA.

Chad Myers (C)

Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA.

Brenda J Andrews (BJ)

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada.

Ji-Young Youn (JY)

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 (CM)

Institute for Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada.

Daniela Rotin (D)

Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

W Brent Derry (WB)

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 (JD)

Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

Alan M Moses (AM)

Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.

Iva Pritišanac (I)

Otto-Loewi Research Center, Division of Medicinal Chemistry, Medical University of Graz, Neue Stiftingtalstrabe 6, 8010, Graz, Austria.

Anne-Claude Gingras (AC)

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 (J)

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. Electronic address: jason.moffat@sickkids.ca.

Classifications MeSH