Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.

<h4>Background</h4>The Wave complex activates the Arp2/3 complex, inducing actin polymerization in lamellipodia and membrane ruffles. The Wave complex is composed of five subunits, the smallest of which, Brick1/Hspc300 (Brk1), is the least characterized. We previously reported that, unli...

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Autores principales:	Emmanuel Derivery, Jenny Fink, Davy Martin, Anne Houdusse, Matthieu Piel, Theresia E Stradal, Daniel Louvard, Alexis Gautreau
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8dc5736ac9304d1b8870b35054f5c809
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spelling	oai:doaj.org-article:8dc5736ac9304d1b8870b35054f5c8092021-11-25T06:12:01ZFree Brick1 is a trimeric precursor in the assembly of a functional wave complex.1932-620310.1371/journal.pone.0002462https://doaj.org/article/8dc5736ac9304d1b8870b35054f5c8092008-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18560548/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The Wave complex activates the Arp2/3 complex, inducing actin polymerization in lamellipodia and membrane ruffles. The Wave complex is composed of five subunits, the smallest of which, Brick1/Hspc300 (Brk1), is the least characterized. We previously reported that, unlike the other subunits, Brk1 also exists as a free form.<h4>Principal findings</h4>Here we report that this free form of Brk1 is composed of homotrimers. Using a novel assay in which purified free Brk1 is electroporated into HeLa cells, we were able to follow its biochemical fate in cells and to show that free Brk1 becomes incorporated into the Wave complex. Importantly, incorporation of free Brk1 into the Wave complex was blocked upon inhibition of protein synthesis and incorporated Brk1 was found to associate preferentially with neosynthesized subunits. Brk1 depleted HeLa cells were found to bleb, as were Nap1, Wave2 or ARPC2 depleted cells, suggesting that this blebbing phenotype of Brk1 depleted cells is due to an impairment of the Wave complex function rather than a specific function of free Brk1. Blebs of Brk1 depleted cells were emitted at sites where lamellipodia and membrane ruffles were normally emitted. In Brk1 depleted cells, the electroporation of free Brk1 was sufficient to restore Wave complex assembly and to rescue the blebbing phenotype.<h4>Conclusion</h4>Together these results establish that the free form of Brk1 is an essential precursor in the assembly of a functional Wave complex.Emmanuel DeriveryJenny FinkDavy MartinAnne HoudusseMatthieu PielTheresia E StradalDaniel LouvardAlexis GautreauPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 6, p e2462 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emmanuel Derivery Jenny Fink Davy Martin Anne Houdusse Matthieu Piel Theresia E Stradal Daniel Louvard Alexis Gautreau Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.
description	<h4>Background</h4>The Wave complex activates the Arp2/3 complex, inducing actin polymerization in lamellipodia and membrane ruffles. The Wave complex is composed of five subunits, the smallest of which, Brick1/Hspc300 (Brk1), is the least characterized. We previously reported that, unlike the other subunits, Brk1 also exists as a free form.<h4>Principal findings</h4>Here we report that this free form of Brk1 is composed of homotrimers. Using a novel assay in which purified free Brk1 is electroporated into HeLa cells, we were able to follow its biochemical fate in cells and to show that free Brk1 becomes incorporated into the Wave complex. Importantly, incorporation of free Brk1 into the Wave complex was blocked upon inhibition of protein synthesis and incorporated Brk1 was found to associate preferentially with neosynthesized subunits. Brk1 depleted HeLa cells were found to bleb, as were Nap1, Wave2 or ARPC2 depleted cells, suggesting that this blebbing phenotype of Brk1 depleted cells is due to an impairment of the Wave complex function rather than a specific function of free Brk1. Blebs of Brk1 depleted cells were emitted at sites where lamellipodia and membrane ruffles were normally emitted. In Brk1 depleted cells, the electroporation of free Brk1 was sufficient to restore Wave complex assembly and to rescue the blebbing phenotype.<h4>Conclusion</h4>Together these results establish that the free form of Brk1 is an essential precursor in the assembly of a functional Wave complex.
format	article
author	Emmanuel Derivery Jenny Fink Davy Martin Anne Houdusse Matthieu Piel Theresia E Stradal Daniel Louvard Alexis Gautreau
author_facet	Emmanuel Derivery Jenny Fink Davy Martin Anne Houdusse Matthieu Piel Theresia E Stradal Daniel Louvard Alexis Gautreau
author_sort	Emmanuel Derivery
title	Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.
title_short	Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.
title_full	Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.
title_fullStr	Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.
title_full_unstemmed	Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.
title_sort	free brick1 is a trimeric precursor in the assembly of a functional wave complex.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/8dc5736ac9304d1b8870b35054f5c809
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Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.

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