Alteration of the proteostasis network of plant cells promotes the post-endoplasmic reticulum trafficking of recombinant mutant (L444P) human β-glucocerebrosidase
Identifieur interne : 001723 ( Ncbi/Checkpoint ); précédent : 001722; suivant : 001724Alteration of the proteostasis network of plant cells promotes the post-endoplasmic reticulum trafficking of recombinant mutant (L444P) human β-glucocerebrosidase
Auteurs : Gholamreza Babajani ; Allison R. KermodeSource :
- Plant Signaling & Behavior [ 1559-2316 ] ; 2014.
Abstract
Gaucher disease is a prevalent lysosomal storage disease characterized by a deficiency in the activity of lysosomal acid β-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45). One of the most prevalent disease-causing mutations in humans is a L444P missense mutation in the GCase protein, which results in its disrupted folding in the endoplasmic reticulum (ER) and impaired post-ER trafficking. To determine whether the post-ER trafficking of this severely malfolded protein can be restored, we expressed the mutant L444P GCase as a recombinant protein in transgenic tobacco (
Url:
DOI: 10.4161/psb.28714
PubMed: 24713615
PubMed Central: 4091198
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000648
- to stream Pmc, to step Curation: 000648
- to stream Pmc, to step Checkpoint: 000534
- to stream Ncbi, to step Merge: 001723
- to stream Ncbi, to step Curation: 001723
Links to Exploration step
PMC:4091198Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Alteration of the proteostasis network of plant cells promotes the post-endoplasmic reticulum trafficking of recombinant mutant (L444P) human β-glucocerebrosidase</title>
<author><name sortKey="Babajani, Gholamreza" sort="Babajani, Gholamreza" uniqKey="Babajani G" first="Gholamreza" last="Babajani">Gholamreza Babajani</name>
</author>
<author><name sortKey="Kermode, Allison R" sort="Kermode, Allison R" uniqKey="Kermode A" first="Allison R" last="Kermode">Allison R. Kermode</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24713615</idno>
<idno type="pmc">4091198</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091198</idno>
<idno type="RBID">PMC:4091198</idno>
<idno type="doi">10.4161/psb.28714</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000648</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000648</idno>
<idno type="wicri:Area/Pmc/Curation">000648</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000648</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000534</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000534</idno>
<idno type="wicri:Area/Ncbi/Merge">001723</idno>
<idno type="wicri:Area/Ncbi/Curation">001723</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">001723</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Alteration of the proteostasis network of plant cells promotes the post-endoplasmic reticulum trafficking of recombinant mutant (L444P) human β-glucocerebrosidase</title>
<author><name sortKey="Babajani, Gholamreza" sort="Babajani, Gholamreza" uniqKey="Babajani G" first="Gholamreza" last="Babajani">Gholamreza Babajani</name>
</author>
<author><name sortKey="Kermode, Allison R" sort="Kermode, Allison R" uniqKey="Kermode A" first="Allison R" last="Kermode">Allison R. Kermode</name>
</author>
</analytic>
<series><title level="j">Plant Signaling & Behavior</title>
<idno type="ISSN">1559-2316</idno>
<idno type="eISSN">1559-2324</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Gaucher disease is a prevalent lysosomal storage disease characterized by a deficiency in the activity of lysosomal acid β-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45). One of the most prevalent disease-causing mutations in humans is a L444P missense mutation in the GCase protein, which results in its disrupted folding in the endoplasmic reticulum (ER) and impaired post-ER trafficking. To determine whether the post-ER trafficking of this severely malfolded protein can be restored, we expressed the mutant L444P GCase as a recombinant protein in transgenic tobacco (<italic>Nicotiana tabacum</italic>
L. cv Bright Yellow 2 [BY2]) cells, in which the GCase variant was equipped with a plant signal peptide to allow for secretion upon rescued trafficking out of the ER. The recombinant L444P mutant GCase was retained in the plant endoplasmic reticulum (ER). Kifunensine and Eeyarestatin I, both inhibitors of ER-associated degradation (ERAD), and the proteostasis regulators, celastrol and MG-132, increased the steady-state levels of the mutant protein inside the plant cells and further promoted the post-ER trafficking of L444P GCase, as indicated by endoglycosidase-H sensitivity- and secretion- analyses. Transcript profiling of genes encoding ER-molecular chaperones, ER stress responsive proteins, and cytoplasmic heat shock response proteins, revealed insignificant or only very modest changes in response to the ERAD inhibitors and proteostasis regulators. An exception was the marked response to celastrol which reduced the steady-state levels of cytoplasmic HSP90 transcripts and protein. As HSP90 participates in the targeting of misfolded proteins to the proteasome pathway, its down-modulation in response to celastrol may partly account for the mechanism of improved homeostasis of L444P GCase mediated by this triterpene.</p>
</div>
</front>
</TEI>
<affiliations><list></list>
<tree><noCountry><name sortKey="Babajani, Gholamreza" sort="Babajani, Gholamreza" uniqKey="Babajani G" first="Gholamreza" last="Babajani">Gholamreza Babajani</name>
<name sortKey="Kermode, Allison R" sort="Kermode, Allison R" uniqKey="Kermode A" first="Allison R" last="Kermode">Allison R. Kermode</name>
</noCountry>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Ncbi/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001723 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Checkpoint/biblio.hfd -nk 001723 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Canada |area= ParkinsonCanadaV1 |flux= Ncbi |étape= Checkpoint |type= RBID |clé= PMC:4091198 |texte= Alteration of the proteostasis network of plant cells promotes the post-endoplasmic reticulum trafficking of recombinant mutant (L444P) human β-glucocerebrosidase }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Checkpoint/RBID.i -Sk "pubmed:24713615" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Checkpoint/biblio.hfd \ | NlmPubMed2Wicri -a ParkinsonCanadaV1
This area was generated with Dilib version V0.6.29. |