Topic
Retromer
About: Retromer is a research topic. Over the lifetime, 642 publications have been published within this topic receiving 36552 citations. The topic is also known as: retromer complex & GO:0030904.
Papers published on a yearly basis
Papers
TL;DR: This study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.
Abstract: The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.
905 citations
TL;DR: A central role for a 'tubular endosomal network' in sorting to recycling pathways that lead not only to the trans-Golgi network but also to different plasma-membrane domains and to specialized storage vesicles is proposed.
Abstract: A subset of intracellular transmembrane proteins such as acid-hydrolase receptors, processing peptidases and SNAREs, as well as extracellular protein toxins such as Shiga toxin and ricin, undergoes 'retrograde' transport from endosomes to the trans-Golgi network. Here, we discuss recent studies that have begun to unravel the molecular machinery that is involved in this process. We also propose a central role for a 'tubular endosomal network' in sorting to recycling pathways that lead not only to the trans-Golgi network but also to different plasma-membrane domains and to specialized storage vesicles.
699 citations
TL;DR: Overall, this work provides a genome-scale, quantitative resource of the impact of the loss of each host gene on fitness/response to viral infection.
586 citations
TL;DR: The endosomal-lysosomal system is emerging as a central player in a host of neurodegenerative diseases, demonstrating potential roles which are likely to be revealed in pathogenesis and for viable therapeutic strategies.
Abstract: The endosomal-lysosomal system is made up of a set of intracellular membranous compartments that dynamically interconvert, which is comprised of early endosomes, recycling endosomes, late endosomes, and the lysosome. In addition, autophagosomes execute autophagy, which delivers intracellular contents to the lysosome. Maturation of endosomes and/or autophagosomes into a lysosome creates an unique acidic environment within the cell for proteolysis and recycling of unneeded cellular components into usable amino acids and other biomolecular building blocks. In the endocytic pathway, gradual maturation of endosomes into a lysosome and acidification of the late endosome are accompanied by vesicle trafficking, protein sorting and targeted degradation of some sorted cargo. Two opposing sorting systems are operating in these processes: the endosomal sorting complex required for transport (ESCRT) supports targeted degradation and the retromer supports retrograde retrieval of certain cargo. The endosomal-lysosomal system is emerging as a central player in a host of neurodegenerative diseases, demonstrating potential roles which are likely to be revealed in pathogenesis and for viable therapeutic strategies. Here we focus on the physiological process of endosomal-lysosomal maturation, acidification and sorting systems along the endocytic pathway, and further discuss relationships between abnormalities in the endosomal-lysosomal system and neurodegenerative diseases, especially Alzheimer’s disease (AD).
579 citations
TL;DR: It is shown that WASH generates an actin network on a restricted domain of sorting and recycling endosomes and that the WASH molecular machine, integrating CP with a NPF, controls the fission of endosome through an interplay between the forces generated by microtubule motors and actin polymerization.
576 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 14 |
| 2024 | 48 |
| 2023 | 49 |
| 2022 | 99 |
| 2021 | 61 |
| 2020 | 58 |