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EMBO J. 2018 Jul 2;37(13). pii: e97706. doi: 10.15252/embj.201797706. Epub 2018 May 29.

The trimeric coiled-coil HSBP1 protein promotes WASH complex assembly at centrosomes.

Author information

1
Ecole Polytechnique, CNRS UMR7654, Université Paris-Saclay, Palaiseau, France.
2
Beatson Institute for Cancer Research, Bearsden, UK.
3
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, Gif-sur-Yvette, France.
4
Pharmacogenomics Unit, Department of Genetics, Institut Curie, Paris, France.
5
Laboratory of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia.
6
Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia.
7
Department of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia.
8
Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Moscow, Russia.
9
Ecole Polytechnique, CNRS UMR7654, Université Paris-Saclay, Palaiseau, France alexis.gautreau@polytechnique.edu.
10
School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia.

Abstract

The Arp2/3 complex generates branched actin networks that exert pushing forces onto different cellular membranes. WASH complexes activate Arp2/3 complexes at the surface of endosomes and thereby fission transport intermediates containing endocytosed receptors, such as α5β1 integrins. How WASH complexes are assembled in the cell is unknown. Here, we identify the small coiled-coil protein HSBP1 as a factor that specifically promotes the assembly of a ternary complex composed of CCDC53, WASH, and FAM21 by dissociating the CCDC53 homotrimeric precursor. HSBP1 operates at the centrosome, which concentrates the building blocks. HSBP1 depletion in human cancer cell lines and in Dictyostelium amoebae phenocopies WASH depletion, suggesting a critical role of the ternary WASH complex for WASH functions. HSBP1 is required for the development of focal adhesions and of cell polarity. These defects impair the migration and invasion of tumor cells. Overexpression of HSBP1 in breast tumors is associated with increased levels of WASH complexes and with poor prognosis for patients.

KEYWORDS:

Arp2/3 complex; actin cytoskeleton; cell migration and invasion; centrosome; multiprotein complex assembly

PMID:
29844016
PMCID:
PMC6028030
[Available on 2019-07-02]
DOI:
10.15252/embj.201797706

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