DPCD is a regulator of R2TP in ciliogenesis initiation through Akt signaling

Yu-Qian Mao; Thiago V. Seraphim; Yimei Wan; Ruikai Wu; Etienne Coyaud; Muhammad Bin Munim; Antonio Mollica; Estelle Laurent; Mohan Babu; Vito Mennella; Brian Raught; Walid A. Houry

Cell Reports (Feb 2024)

DPCD is a regulator of R2TP in ciliogenesis initiation through Akt signaling

Yu-Qian Mao,
Thiago V. Seraphim,
Yimei Wan,
Ruikai Wu,
Etienne Coyaud,
Muhammad Bin Munim,
Antonio Mollica,
Estelle Laurent,
Mohan Babu,
Vito Mennella,
Brian Raught,
Walid A. Houry

Affiliations

Yu-Qian Mao: Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada
Thiago V. Seraphim: Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada; Department of Chemistry and Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada
Yimei Wan: Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada
Ruikai Wu: Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada
Etienne Coyaud: Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada
Muhammad Bin Munim: Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada
Antonio Mollica: Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada
Estelle Laurent: Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada
Mohan Babu: Department of Chemistry and Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada
Vito Mennella: Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada; Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; MRC Toxicology Unit, School of Biological Sciences, University of Cambridge, Cambridge CB2 1QR, UK; Department of Pathology, School of Biological Sciences, University of Cambridge, Cambridge CB2 1QP, UK
Brian Raught: Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada
Walid A. Houry: Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada; Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada; Corresponding author

Journal volume & issue: Vol. 43, no. 2
p. 113713

Abstract

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Summary: R2TP is a chaperone complex consisting of the AAA+ ATPases RUVBL1 and RUVBL2, as well as RPAP3 and PIH1D1 proteins. R2TP is responsible for the assembly of macromolecular complexes mainly acting through different adaptors. Using proximity-labeling mass spectrometry, we identified deleted in primary ciliary dyskinesia (DPCD) as an adaptor of R2TP. Here, we demonstrate that R2TP-DPCD influences ciliogenesis initiation through a unique mechanism by interaction with Akt kinase to regulate its phosphorylation levels rather than its stability. We further show that DPCD is a heart-shaped monomeric protein with two domains. A highly conserved region in the cysteine- and histidine-rich domains-containing proteins and SGT1 (CS) domain of DPCD interacts with the RUVBL2 DII domain with high affinity to form a stable R2TP-DPCD complex both in cellulo and in vitro. Considering that DPCD is one among several CS-domain-containing proteins found to associate with RUVBL1/2, we propose that RUVBL1/2 are CS-domain-binding proteins that regulate complex assembly and downstream signaling.

CP: Cell biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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