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Evolutionary reconstruction of the retromer complex and its function in Trypanosoma brucei
Abstract
Intracellular trafficking and protein sorting are mediated by various protein complexes, with the retromer complex being primarily involved in retrograde traffic from the endosome or lysosome to the Golgi complex. Here, comparative genomics, cell biology and phylogenetics were used to probe the early evolution of retromer and its function. Retromer subunits Vps26, Vps29 and Vps35 are near universal, and, by inference, the complex was an ancient feature of eukaryotic cells. Surprisingly, we found DSCR3, a Vps26 paralogue in humans associated with Down's syndrome, in at least four eukaryotic supergroups, implying a more ancient origin than previously suspected. By contrast, retromer cargo proteins showed considerable interlineage variability, with lineage-specific and broadly conserved examples found. Vps10 trafficking probably represents an ancestral role for the complex. Vps5, the BAR-domain-containing membrane-deformation subunit, was found in diverse eukaryotes, including in the divergent eukaryote Trypanosoma brucei, where it is the first example of a BAR-domain protein. To determine functional conservation, an initial characterisation of retromer was performed in T. brucei; the endosomal localisation and its role in endosomal targeting are conserved. Therefore retromer is identified as a further feature of the sophisticated intracellular trafficking machinery of the last eukaryotic common ancestor, with BAR domains representing a possible third independent mechanism of membrane-deformation arising in early eukaryotes.
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C16orf62 carboxy-terminal region (residues 717-1030) is predicted with 99.8% probability to contain a HEAT-repeat protein fold similar to VPS35.
“Using HHPred, we noted that the carboxy-terminal region (residues 717-1030) of human C16orf62 is predicted, with 99.8% probability, to contain a HEAT-repeat protein fold similar to that observed in VPS3542.”
From Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling (2017) · cites this paper as [42]
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Metadata
- Authors
- Koumandou, V. L., Klute, M. J., Herman, E. K., Nunez-Miguel, R., Dacks, J. B., & Field, M. C.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2011-05-01
- Volume
- 124
- Issue
- 9
- Pages
- 1496-1509
- ISSN
- 1477-9137
- 0021-9533
- Cited by
- 109
- References
- 1
- Language
- en
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