Coordinated Assembly of WAVE and WASH complexes
Abstract
WAVE and WASH polymerize Arp2/3-mediated branched actin at the leading edge of migrating cells and on the surface of endosomes, respectively. These two proteins are regulated within similar multiprotein complexes, the assembly mechanism of which remains poorly understood. Here we found using mass spectrometry that the two smallest subunits, BRK1 of the WAVE complex and CCDC53 of the WASH complex, interact with each other and with the assembly factor HSBP1. HSBP1 promotes WAVE and WASH assemblies and their respective activities, migration persistence and endosomal branched actin. Reduced levels of WAVE and WASH complexes caused by HSBP1 depletion can be corrected by providing cells with an excess of BRK1 or CCDC53 to assemble their specific complex. Unexpectedly, endogenous levels of BRK1 cross-regulate WASH assembly, whereas those of CCDC53 crossregulate WAVE assembly. We found that various oligomers comprising BRK1, CCDC53 and HSBP1, including a heterotrimer containing one molecule of each, are formed through their promiscuous coiled coils. These oligomers play a coordinating role in the assembly of WAVE and WASH complexes.
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BibTeX
@misc{novikov2026coordinated,
title = {{Coordinated Assembly of WAVE and WASH complexes}},
author = {Nikita M Novikov and Christine Lazennec-Schurdevin and Peter A Thomason and Iman Haddad and Lucile Kogey-Fuchs and Magalie Duchateau and Artem I Fokin and Daria Bondar and Nicolas Dugave and Sergio Lilla and Julia Chamot-Rooke and Joëlle Vinh and Raphaël Guérois and Yves Mechulam and Robert H Insall and Emmanuelle Schmitt and Alexis M Gautreau},
howpublished = {HAL},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.752629},
url = {https://hal.science/hal-05763428v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Coordinated Assembly of WAVE and WASH complexes
AU - Nikita M Novikov
AU - Christine Lazennec-Schurdevin
AU - Peter A Thomason
AU - Iman Haddad
AU - Lucile Kogey-Fuchs
AU - Magalie Duchateau
AU - Artem I Fokin
AU - Daria Bondar
AU - Nicolas Dugave
AU - Sergio Lilla
AU - Julia Chamot-Rooke
AU - Joëlle Vinh
AU - Raphaël Guérois
AU - Yves Mechulam
AU - Robert H Insall
AU - Emmanuelle Schmitt
AU - Alexis M Gautreau
PY - 2026
DA - 2026/09/18
PB - HAL
DO - 10.64898/2026.09.18.752629
UR - https://hal.science/hal-05763428v1
AB - WAVE and WASH polymerize Arp2/3-mediated branched actin at the leading edge of migrating cells and on the surface of endosomes, respectively. These two proteins are regulated within similar multiprotein complexes, the assembly mechanism of which remains poorly understood. Here we found using mass spectrometry that the two smallest subunits, BRK1 of the WAVE complex and CCDC53 of the WASH complex, interact with each other and with the assembly factor HSBP1. HSBP1 promotes WAVE and WASH assemblies and their respective activities, migration persistence and endosomal branched actin. Reduced levels of WAVE and WASH complexes caused by HSBP1 depletion can be corrected by providing cells with an excess of BRK1 or CCDC53 to assemble their specific complex. Unexpectedly, endogenous levels of BRK1 cross-regulate WASH assembly, whereas those of CCDC53 crossregulate WAVE assembly. We found that various oligomers comprising BRK1, CCDC53 and HSBP1, including a heterotrimer containing one molecule of each, are formed through their promiscuous coiled coils. These oligomers play a coordinating role in the assembly of WAVE and WASH complexes.
ER -