ArticlePloS one2013
The intracellular domain of sortilin interacts with amyloid precursor protein and regulates its lysosomal and lipid raft trafficking.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Transmembrane domain interactions underlie NSG1 regulation of sortilin ectodomain shedding.The Journal of biological chemistry · 2025Article
- Plasma and CSF Amyloid-β42 Predict Plasma Sortilin, Which Influences Cognitive Impairment via Mediation of Whole-Brain Volume: A 12-Month Longitudinal Study Across the Alzheimer's Disease Spectrum.Journal of molecular neuroscience : MN · 2025Article
- Endosomal trafficking and related genetic underpinnings as a hub in Alzheimer's disease.Journal of cellular physiology · 2022Review
- AP-4 regulates neuronal lysosome composition, function, and transport via regulating export of critical lysosome receptor proteins at the trans-Golgi network.Molecular biology of the cell · 2022Article
- The emerging role of furin in neurodegenerative and neuropsychiatric diseases.Translational neurodegeneration · 2022Review
- Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage.Cell communication and signaling : CCS · 2021Article
- Involvement of Lipids in Alzheimer's Disease Pathology and Potential Therapies.Frontiers in physiology · 2020Review
- Cellular Trafficking of Amyloid Precursor Protein in Amyloidogenesis Physiological and Pathological Significance.Molecular neurobiology · 2019Review
- Regional and Cellular Mapping of Sortilin Immunoreactivity in Adult Human Brain.Frontiers in neuroanatomy · 2019Article
- Trafficking in Alzheimer's Disease: Modulation of APP Transport and Processing by the Transmembrane Proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin.Molecular neurobiology · 2018Review
- Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA.Cellular and molecular life sciences : CMLS · 2018Article
- Dysregulation of Neuronal Iron Homeostasis as an Alternative Unifying Effect of Mutations Causing Familial Alzheimer's Disease.Frontiers in neuroscience · 2018Article
- Informatics Support for Basic Research in Biomedicine.ILAR journal · 2017Review
- Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum.Frontiers in neuroanatomy · 2017Article
- Sortilin mediates vascular calcification via its recruitment into extracellular vesicles.The Journal of clinical investigation · 2016Article
- Neuronal-Targeted TFEB Accelerates Lysosomal Degradation of APP, Reducing Aβ Generation and Amyloid Plaque Pathogenesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other.The Journal of biological chemistry · 2015Article
- PAT1 inversely regulates the surface Amyloid Precursor Protein level in mouse primary neurons.BMC neuroscience · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The processing of Amyloid precursor protein (APP) is multifaceted, comprising of protein transport, internalization and sequential proteolysis. However, the exact mechanism of APP intracellular trafficking and distribution remains unclear. To determine the interaction between sortilin and APP and the effect of sortilin on APP trafficking and processing, we studied the binding site and its function by mapping experiments, colocalization, coimmunoprecipitation and sucrose gradient fractionation. We identified for the first time that sortilin interacts with APP at both N- and C-terminal regions. The sortilin-FLVHRY (residues 787-792) and APP-NPTYKFFE (residues 759-766) motifs are crucial for the C-terminal interaction. We also found that lack of the FLVHRY motif reduces APP lysosomal targeting and increases APP distribution in lipid rafts in co-transfected HEK293 cells. These results are consistent with our in vivo data where sortilin knockout mice showed a decrease of APP lysosomal distribution and an increase of APP in lipid rafts. We further confirmed that overexpression of sortilin-FLVHRY mutants failed to rescue the lysosomal degradation of APP. Thus, our data suggests that sortilin is implicated in APP lysosomal and lipid raft targeting via its carboxyl-terminal F/YXXXXF/Y motif. Our study provides new molecular insights into APP trafficking and processing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.