ArticleMolecular neurodegeneration2006
Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel gamma-secretase substrates.
Article in Molecular neurodegeneration, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- SorCS1 inhibits amyloid-β binding to neurexin and rescues amyloid-β-induced synaptic pathology.Life science alliance · 2023Article
- Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage.Cell communication and signaling : CCS · 2021Article
- Brain transcriptome analysis reveals subtle effects on mitochondrial function and iron homeostasis of mutations in the SORL1 gene implicated in early onset familial Alzheimer's disease.Molecular brain · 2020Article
- Sorting Out the Role of theJournal of Alzheimer's disease reports · 2020Review
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- Inter-Species Differences in Regulation of the Progranulin-Sortilin Axis in TDP-43 Cell Models of Neurodegeneration.International journal of molecular sciences · 2019Article
- Lysosome biogenesis in health and disease.Journal of neurochemistry · 2019Review
- HSPA12A targets the cytoplasmic domain and affects the trafficking of the Amyloid Precursor Protein receptor SorLA.Scientific reports · 2019Article
- Nerve Growth Factor Pathobiology During the Progression of Alzheimer's Disease.Frontiers in neuroscience · 2019Review
- Targeting γ-secretase triggers the selective enrichment of oligomeric APP-CTFs in brain extracellular vesicles from Alzheimer cell and mouse models.Translational neurodegeneration · 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 of sortilin regulates its trafficking to extracellular vesicles.The Journal of biological chemistry · 2018Article
- Regulatory Roles of Sortilin and SorLA in Immune-Related Processes.Frontiers in pharmacology · 2018Review
- Genetic epistasis regulates amyloid deposition in resilient aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017Article
- Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum.Frontiers in neuroanatomy · 2017Article
- Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer's Disease Patients Carrying the APOE Epsilon 4 Allele.Neural plasticity · 2017Article
- Focal Adhesion Kinase-Dependent Role of the Soluble Form of Neurotensin Receptor-3/Sortilin in Colorectal Cancer Cell Dissociation.International journal of molecular sciences · 2016Review
- SorLA complement-type repeat domains protect the amyloid precursor protein against processing.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe mammalian Vps10p sorting receptor family is a group of 5 type I membrane homologs (Sortilin, SorLA, and SorCS1-3). These receptors bind various cargo proteins via their luminal Vps10p domains and have been shown to mediate a variety of intracellular sorting and trafficking functions. These proteins are highly expressed in the brain. SorLA has been shown to be down regulated in Alzheimer's disease brains, interact with ApoE, and modulate Abeta production. Sortilin has been shown to be part of proNGF mediated death signaling that results from a complex of Sortilin, p75NTR and proNGF. We have investigated and provide evidence for gamma-secretase cleavage of this family of proteins.
resultsWe provide evidence that these receptors are substrates for presenilin dependent gamma-secretase cleavage. Gamma-secretase cleavage of these sorting receptors is inhibited by gamma-secretase inhibitors and does not occur in PS1/PS2 knockout cells. Like most gamma-secretase substrates, we find that ectodomain shedding precedes gamma-secretase cleavage. The ectodomain cleavage is inhibited by a metalloprotease inhibitor and activated by PMA suggesting that it is mediated by an alpha-secretase like cleavage.
conclusionThese data indicate that the alpha- and gamma-secretase cleavages of the mammalian Vps10p sorting receptors occur in a fashion analogous to other known gamma-secretase substrates, and could possibly regulate the biological functions of these proteins.
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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.