Show simple item record

dc.contributor.authorBoehm, Cordula M.
dc.contributor.authorObado, Samson
dc.contributor.authorGadelha, Catarina
dc.contributor.authorKaupisch, Alexandra
dc.contributor.authorManna, Paul T.
dc.contributor.authorGould, Gwyn W.
dc.contributor.authorMunson, Mary
dc.contributor.authorChait, Brian T.
dc.contributor.authorRout, Michael P.
dc.contributor.authorField, Mark C.
dc.date2022-08-11T08:09:47.000
dc.date.accessioned2022-08-23T16:43:18Z
dc.date.available2022-08-23T16:43:18Z
dc.date.issued2017-01-23
dc.date.submitted2017-06-01
dc.identifier.citationPLoS Pathog. 2017 Jan 23;13(1):e1006063. eCollection 2017 Jan. <a href="https://doi.org/10.1371/journal.ppat.1006063">Link to article on publisher's site</a>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1006063
dc.identifier.pmid28114397
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40264
dc.description.abstractMembrane transport is an essential component of pathogenesis for most infectious organisms. In African trypanosomes, transport to and from the plasma membrane is closely coupled to immune evasion and antigenic variation. In mammals and fungi an octameric exocyst complex mediates late steps in exocytosis, but comparative genomics suggested that trypanosomes retain only six canonical subunits, implying mechanistic divergence. We directly determined the composition of the Trypanosoma brucei exocyst by affinity isolation and demonstrate that the parasite complex is nonameric, retaining all eight canonical subunits (albeit highly divergent at the sequence level) plus a novel essential subunit, Exo99. Exo99 and Sec15 knockdowns have remarkably similar phenotypes in terms of viability and impact on morphology and trafficking pathways. Significantly, both Sec15 and Exo99 have a clear function in endocytosis, and global proteomic analysis indicates an important role in maintaining the surface proteome. Taken together these data indicate additional exocyst functions in trypanosomes, which likely include endocytosis, recycling and control of surface composition. Knockdowns in HeLa cells suggest that the role in endocytosis is shared with metazoan cells. We conclude that, whilst the trypanosome exocyst has novel components, overall functionality appears conserved, and suggest that the unique subunit may provide therapeutic opportunities.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=28114397&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsCopyright © 2017 Boehm et al.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectImmunopathology
dc.subjectMicrobiology
dc.titleThe Trypanosome Exocyst: A Conserved Structure Revealing a New Role in Endocytosis
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume13
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4064&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3059
dc.identifier.contextkey10236385
refterms.dateFOA2022-08-23T16:43:18Z
html.description.abstract<p>Membrane transport is an essential component of pathogenesis for most infectious organisms. In African trypanosomes, transport to and from the plasma membrane is closely coupled to immune evasion and antigenic variation. In mammals and fungi an octameric exocyst complex mediates late steps in exocytosis, but comparative genomics suggested that trypanosomes retain only six canonical subunits, implying mechanistic divergence. We directly determined the composition of the Trypanosoma brucei exocyst by affinity isolation and demonstrate that the parasite complex is nonameric, retaining all eight canonical subunits (albeit highly divergent at the sequence level) plus a novel essential subunit, Exo99. Exo99 and Sec15 knockdowns have remarkably similar phenotypes in terms of viability and impact on morphology and trafficking pathways. Significantly, both Sec15 and Exo99 have a clear function in endocytosis, and global proteomic analysis indicates an important role in maintaining the surface proteome. Taken together these data indicate additional exocyst functions in trypanosomes, which likely include endocytosis, recycling and control of surface composition. Knockdowns in HeLa cells suggest that the role in endocytosis is shared with metazoan cells. We conclude that, whilst the trypanosome exocyst has novel components, overall functionality appears conserved, and suggest that the unique subunit may provide therapeutic opportunities.</p>
dc.identifier.submissionpathoapubs/3059
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pagese1006063


Files in this item

Thumbnail
Name:
ppat.1006063.pdf
Size:
2.834Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

Copyright © 2017 Boehm et al.
Except where otherwise noted, this item's license is described as Copyright © 2017 Boehm et al.