Clancy, Anne

[["dc.bibliographiccitation.artnumber","e59590"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Leznicki, Pawel"],["dc.contributor.author","Roebuck, Quentin P."],["dc.contributor.author","Wunderley, Lydia"],["dc.contributor.author","Clancy, Anne"],["dc.contributor.author","Krysztofinska, Ewelina M."],["dc.contributor.author","Isaacson, Rivka L."],["dc.contributor.author","Warwicker, Jim"],["dc.contributor.author","Schwappach, Blanche"],["dc.contributor.author","High, Stephen"],["dc.date.accessioned","2017-09-07T11:47:44Z"],["dc.date.available","2017-09-07T11:47:44Z"],["dc.date.issued","2013"],["dc.description.abstract","Background: The BAG6 protein is a subunit of a heterotrimeric complex that binds a range of membrane and secretory protein precursors localized to the cytosol, enforcing quality control and influencing their subsequent fate. Methodology and Principal Findings: BAG6 has an N-terminal ubiquitin-like domain, and a C-terminal Bcl-2-associated athanogene domain, separated by a large central proline-rich region. We have used in vitro binding approaches to identify regions of BAG6 important for its interactions with: i) the small-glutamine rich tetratricopeptide repeat-containing protein alpha (SGTA) and ii) two model tail-anchored membrane proteins as a paradigm for its hydrophobic substrates. We show that the BAG6-UBL is essential for binding to SGTA, and find that the UBL of a second subunit of the BAG6-complex, ubiquitin-like protein 4A (UBL4A), competes for SGTA binding. Our data show that this binding is selective, and suggest that SGTA can bind either BAG6, or UBL4A, but not both at the same time. We adapted our in vitro binding assay to study the association of BAG6 with an immobilized tail-anchored protein, Sec61b, and find both the UBL and BAG domains are dispensable for binding this substrate. This conclusion was further supported using a heterologous subcellular localization assay in yeast, where the BAG6-dependent nuclear relocalization of a second tail-anchored protein, GFP-Sed5, also required neither the UBL, nor the BAG domain of BAG6. Significance: On the basis of these findings, we propose a working model where the large central region of the BAG6 protein provides a binding site for a diverse group of substrates, many of which expose a hydrophobic stretch of polypeptide. This arrangement would enable the BAG6 complex to bring together its substrates with potential effectors including those recruited via its N-terminal UBL. Such effectors may include SGTA, and the resulting assemblies influence the subsequent fate of the hydrophobic BAG6 substrates."],["dc.identifier.doi","10.1371/journal.pone.0059590"],["dc.identifier.gro","3142369"],["dc.identifier.isi","000316549400072"],["dc.identifier.pmid","23533635"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8748"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7519"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","The Association of BAG6 with SGTA and Tail-Anchored Proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2170"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Journal of Cell Science"],["dc.bibliographiccitation.lastpage","2178"],["dc.bibliographiccitation.volume","123"],["dc.contributor.author","Leznicki, Pawel"],["dc.contributor.author","Clancy, Anne"],["dc.contributor.author","Schwappach, Blanche"],["dc.contributor.author","High, Stephen"],["dc.date.accessioned","2017-09-07T11:45:57Z"],["dc.date.available","2017-09-07T11:45:57Z"],["dc.date.issued","2010"],["dc.description.abstract","The membrane integration of tail-anchored proteins at the endoplasmic reticulum (ER) is post-translational, with different tail-anchored proteins exploiting distinct cytosolic factors. For example, mammalian TRC40 has a well-defined role during delivery of tail-anchored proteins to the ER. Although its Saccharomyces cerevisiae equivalent, Get3, is known to function in concert with at least four other components, Get1, Get2, Get4 and Get5 (Mdy2), the role of additional mammalian proteins during tail-anchored protein biogenesis is unclear. To this end, we analysed the cytosolic binding partners of Sec61 beta, a well-defined substrate of TRC40, and identified Bat3 as a previously unknown interacting partner. Depletion of Bat3 inhibits the membrane integration of Sec61 beta, but not of a second, TRC40-independent, tail-anchored protein, cytochrome b5. Thus, Bat3 influences the in vitro membrane integration of tail-anchored proteins using the TRC40 pathway. When expressed in Saccharomyces cerevisiae lacking a functional GET pathway for tail-anchored protein biogenesis, Bat3 associates with the resulting cytosolic pool of non-targeted chains and diverts it to the nucleus. This Bat3-mediated mislocalisation is not dependent upon Sgt2, a recently identified component of the yeast GET pathway, and we propose that Bat3 either modulates the TRC40 pathway in higher eukaryotes or provides an alternative fate for newly synthesised tail-anchored proteins."],["dc.identifier.doi","10.1242/jcs.066738"],["dc.identifier.gro","3142898"],["dc.identifier.isi","000278856400004"],["dc.identifier.pmid","20516149"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/353"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Wellcome Trust"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1477-9137"],["dc.relation.issn","0021-9533"],["dc.title","Bat3 promotes the membrane integration of tail-anchored proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]