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Early endosomes sort transmembrane cargo either for lysosomal degradation or retrieval to the plasma membrane or the Golgi complex. Endosomal retrieval in eukaryotes is governed by the anciently homologous retromer or retriever complexes. Each comprises a core tri-protein subcomplex, membrane-deformation proteins and interacting partner complexes, together retrieving a variety of known cargo proteins. Trichomonas vaginalis, a sexually transmitted human parasite, uses the endomembrane system for pathogenesis. It has massively and selectively expanded its endomembrane protein complement, the evolutionary path of which has been largely unexplored. Our molecular evolutionary study of retromer, retriever and associated machinery in parabasalids and its free-living sister lineage of Anaeramoeba demonstrates specific expansion of the retromer machinery, contrasting with the retriever components. We also observed partial loss of the Commander complex and sorting nexins in Parabasalia but complete retention in Anaeramoeba. Notably, we identified putative parabasalid sorting nexin analogs. Finally, we report the first retriever protein localization in a non-metazoan group along with retromer protein localization in T. vaginalis.
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http://dx.doi.org/10.1242/jcs.261949 | DOI Listing |
J Cell Biol
November 2025
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Two major protein recycling pathways have emerged as key regulators of enduring forms of synaptic plasticity, such as long-term potentiation (LTP), yet how these pathways are recruited during plasticity is unknown. Phosphatidylinositol-3-phosphate (PI(3)P) is a key regulator of endosomal trafficking and alterations in this lipid have been linked to neurodegeneration. Here, using primary hippocampal neurons, we demonstrate dynamic PI(3)P synthesis during chemical induction of LTP (cLTP), which drives coordinate recruitment of the SNX17-Retriever and SNX27-Retromer pathways to endosomes and synaptic sites.
View Article and Find Full Text PDFNat Commun
July 2025
School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol, UK.
Endosomal retrieval and recycling of integral cargo proteins is essential for cell and organism development and homeostasis and is orchestrated through a specialised endosomal nanodomain, the retrieval sub-domain. Sub-domain dysfunction is associated with human disease, but our mechanistic understanding of its function remains poorly described. Here, using proximity proteomics of retrieval sub-domain components Retromer and Retriever we identify mechanistic details of retrieval sub-domain composition and organization, including an unrecognised complexity in the interface with RAB GTPase switching.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
July 2025
School of Biochemistry, Faculty of Health and Life Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
The endosomal-lysosomal network is a hub of organelles that orchestrate the dynamic sorting of hundreds of integral membrane proteins to maintain cellular homeostasis. VPS29 is a central conductor of this network through its assembly into Retromer, Retriever, and Commander endosomal sorting complexes, and its role in regulating RAB GTPase activity. Two VPS29 isoforms have been described, VPS29A and VPS29B, that differ solely in their amino-terminal sequences.
View Article and Find Full Text PDFCell Biol Int
August 2025
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Within endosomes cargo proteins are sorted and packaged into endosomal-transport carriers (ETCs) enabling their delivery to other intracellular compartments. Retromer, a conserved multimeric protein complex, has defined functions in sorting cargo mediating formation of ETCs for both retrograde trafficking back to the trans-Golgi network (TGN) and recycling of cargo to the cell surface. Recent studies have identified the retriever complex, which is structurally like retromer, that also can function in the recycling of cargo from endosomes.
View Article and Find Full Text PDFPlants (Basel)
September 2024
Department of Plant Biology, University of Vermont, Burlington, VT 05405, USA.
The tight regulation of protein composition within the plasma membranes of plant cells is crucial for the proper development of plants and for their ability to respond to a changing environment. Upon being endocytosed, integral membrane proteins can be secreted, sorted into multivesicular bodies/late endosomes, and degraded in the lytic vacuole, or recycled back to the plasma membrane to continue functioning. The evolutionarily conserved retromer complex has attracted the interest of plant cell biologists for over a decade as it has emerged as a key regulator of the trafficking of endocytosed integral plasma membrane proteins.
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