RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils
Identifieur interne : 000516 ( Main/Exploration ); précédent : 000515; suivant : 000517RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils
Auteurs : Nava Zaarur [États-Unis] ; Xiaobin Xu [États-Unis] ; Patrick Lestienne [France] ; Anatoli B. Meriin [États-Unis] ; Mark Mccomb [États-Unis] ; Catherine E. Costello [États-Unis] ; Gary P. Newnam [États-Unis] ; Rakhee Ganti [États-Unis] ; Nina V. Romanova [Russie] ; Maruda Shanmugasundaram [États-Unis] ; Sara Tn Silva [Portugal] ; Tiago M. Bandeiras [Portugal] ; Pedro M. Matias [Portugal] ; Kirill S. Lobachev [États-Unis] ; Igor K. Lednev [États-Unis] ; Yury O. Chernoff [États-Unis, Russie] ; Michael Y. Sherman [États-Unis]Source :
- The EMBO Journal [ 0261-4189 ] ; 2015.
Abstract
The aggresome is an organelle that recruits aggregated proteins for storage and degradation. We performed an siRNA screen for proteins involved in aggresome formation and identified novel mammalian AAA+ protein disaggregases RuvbL1 and RuvbL2. Depletion of RuvbL1 or RuvbL2 suppressed aggresome formation and caused buildup of multiple cytoplasmic aggregates. Similarly, downregulation of RuvbL orthologs in yeast suppressed the formation of an aggresome-like body and enhanced the aggregate toxicity. In contrast, their overproduction enhanced the resistance to proteotoxic stress independently of chaperone Hsp104. Mammalian RuvbL associated with the aggresome, and the aggresome substrate synphilin-1 interacted directly with the RuvbL1 barrel-like structure near the opening of the central channel. Importantly, polypeptides with unfolded structures and amyloid fibrils stimulated the ATPase activity of RuvbL. Finally, disassembly of protein aggregates was promoted by RuvbL. These data indicate that RuvbL complexes serve as chaperones in protein disaggregation.
Url:
DOI: 10.15252/embj.201591245
PubMed: 26303906
PubMed Central: 4570522
Affiliations:
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Le document en format XML
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Atlanta, GA</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="au5"><institution>Laboratory of Amyloid Biology and Institute of Translational Biomedicine, St. Petersburg State University</institution>
<addr-line>St. Petersburg, Russia</addr-line>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>St. Petersburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sherman, Michael Y" sort="Sherman, Michael Y" uniqKey="Sherman M" first="Michael Y" last="Sherman">Michael Y. Sherman</name>
<affiliation wicri:level="2"><nlm:aff id="au1"><institution>Department of Biochemistry, Boston University School of Medicine</institution>
<addr-line>Boston, MA, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">The EMBO Journal</title>
<idno type="ISSN">0261-4189</idno>
<idno type="eISSN">1460-2075</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The aggresome is an organelle that recruits aggregated proteins for storage and degradation. We performed an siRNA screen for proteins involved in aggresome formation and identified novel mammalian AAA+ protein disaggregases RuvbL1 and RuvbL2. Depletion of RuvbL1 or RuvbL2 suppressed aggresome formation and caused buildup of multiple cytoplasmic aggregates. Similarly, downregulation of RuvbL orthologs in yeast suppressed the formation of an aggresome-like body and enhanced the aggregate toxicity. In contrast, their overproduction enhanced the resistance to proteotoxic stress independently of chaperone Hsp104. Mammalian RuvbL associated with the aggresome, and the aggresome substrate synphilin-1 interacted directly with the RuvbL1 barrel-like structure near the opening of the central channel. Importantly, polypeptides with unfolded structures and amyloid fibrils stimulated the ATPase activity of RuvbL. Finally, disassembly of protein aggregates was promoted by RuvbL. These data indicate that RuvbL complexes serve as chaperones in protein disaggregation.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
<li>Portugal</li>
<li>Russie</li>
<li>États-Unis</li>
</country>
<region><li>Géorgie (États-Unis)</li>
<li>Massachusetts</li>
<li>État de New York</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Zaarur, Nava" sort="Zaarur, Nava" uniqKey="Zaarur N" first="Nava" last="Zaarur">Nava Zaarur</name>
</region>
<name sortKey="Chernoff, Yury O" sort="Chernoff, Yury O" uniqKey="Chernoff Y" first="Yury O" last="Chernoff">Yury O. Chernoff</name>
<name sortKey="Costello, Catherine E" sort="Costello, Catherine E" uniqKey="Costello C" first="Catherine E" last="Costello">Catherine E. Costello</name>
<name sortKey="Costello, Catherine E" sort="Costello, Catherine E" uniqKey="Costello C" first="Catherine E" last="Costello">Catherine E. Costello</name>
<name sortKey="Ganti, Rakhee" sort="Ganti, Rakhee" uniqKey="Ganti R" first="Rakhee" last="Ganti">Rakhee Ganti</name>
<name sortKey="Lednev, Igor K" sort="Lednev, Igor K" uniqKey="Lednev I" first="Igor K" last="Lednev">Igor K. Lednev</name>
<name sortKey="Lobachev, Kirill S" sort="Lobachev, Kirill S" uniqKey="Lobachev K" first="Kirill S" last="Lobachev">Kirill S. Lobachev</name>
<name sortKey="Mccomb, Mark" sort="Mccomb, Mark" uniqKey="Mccomb M" first="Mark" last="Mccomb">Mark Mccomb</name>
<name sortKey="Meriin, Anatoli B" sort="Meriin, Anatoli B" uniqKey="Meriin A" first="Anatoli B" last="Meriin">Anatoli B. Meriin</name>
<name sortKey="Newnam, Gary P" sort="Newnam, Gary P" uniqKey="Newnam G" first="Gary P" last="Newnam">Gary P. Newnam</name>
<name sortKey="Shanmugasundaram, Maruda" sort="Shanmugasundaram, Maruda" uniqKey="Shanmugasundaram M" first="Maruda" last="Shanmugasundaram">Maruda Shanmugasundaram</name>
<name sortKey="Sherman, Michael Y" sort="Sherman, Michael Y" uniqKey="Sherman M" first="Michael Y" last="Sherman">Michael Y. Sherman</name>
<name sortKey="Xu, Xiaobin" sort="Xu, Xiaobin" uniqKey="Xu X" first="Xiaobin" last="Xu">Xiaobin Xu</name>
</country>
<country name="France"><noRegion><name sortKey="Lestienne, Patrick" sort="Lestienne, Patrick" uniqKey="Lestienne P" first="Patrick" last="Lestienne">Patrick Lestienne</name>
</noRegion>
</country>
<country name="Russie"><noRegion><name sortKey="Romanova, Nina V" sort="Romanova, Nina V" uniqKey="Romanova N" first="Nina V" last="Romanova">Nina V. Romanova</name>
</noRegion>
<name sortKey="Chernoff, Yury O" sort="Chernoff, Yury O" uniqKey="Chernoff Y" first="Yury O" last="Chernoff">Yury O. Chernoff</name>
</country>
<country name="Portugal"><noRegion><name sortKey="Silva, Sara Tn" sort="Silva, Sara Tn" uniqKey="Silva S" first="Sara Tn" last="Silva">Sara Tn Silva</name>
</noRegion>
<name sortKey="Bandeiras, Tiago M" sort="Bandeiras, Tiago M" uniqKey="Bandeiras T" first="Tiago M" last="Bandeiras">Tiago M. Bandeiras</name>
<name sortKey="Matias, Pedro M" sort="Matias, Pedro M" uniqKey="Matias P" first="Pedro M" last="Matias">Pedro M. Matias</name>
<name sortKey="Matias, Pedro M" sort="Matias, Pedro M" uniqKey="Matias P" first="Pedro M" last="Matias">Pedro M. Matias</name>
</country>
</tree>
</affiliations>
</record>
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