ArticleBiology open2012
Calsyntenin-1 shelters APP from proteolytic processing during anterograde axonal transport.
Article in Biology open, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Membrane trafficking of synaptic adhesion molecules.The Journal of physiology · 2025Review
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration.Science advances · 2022Article
- Article
- Normal levels of KIF5 but reduced KLC1 levels in both Alzheimer disease and Alzheimer disease in Down syndrome: evidence suggesting defects in anterograde transport.Alzheimer's research & therapy · 2021Article
- Kinesin light chain-1 serine-460 phosphorylation is altered in Alzheimer's disease and regulates axonal transport and processing of the amyloid precursor protein.Acta neuropathologica communications · 2019Article
- Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid.Molecular & cellular proteomics : MCP · 2019Article
- The Beta Amyloid Dysfunction (BAD) Hypothesis for Alzheimer's Disease.Frontiers in neuroscience · 2019Article
- A Role forFrontiers in cellular neuroscience · 2019Article
- Calsyntenin-1 Negatively Regulates ICAM5 Accumulation in Postsynaptic Membrane and Influences Dendritic Spine Maturation in a Mouse Model of Fragile X Syndrome.Frontiers in neuroscience · 2019Article
- Regulation of Glutamate Signaling in the Sensorimotor Circuit by CASY-1A/Calsyntenin inGenetics · 2018Article
- The C-terminal of CASY-1/Calsyntenin regulates GABAergic synaptic transmission at the Caenorhabditis elegans neuromuscular junction.PLoS genetics · 2018Article
- EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment.Journal of cell science · 2017Article
- Physiological Functions of the β-Site Amyloid Precursor Protein Cleaving Enzyme 1 and 2.Frontiers in molecular neuroscience · 2017Review
- Calsyntenins Are Expressed in a Dynamic and Partially Overlapping Manner during Neural Development.Frontiers in neuroanatomy · 2017Article
- The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development.Frontiers in cellular neuroscience · 2017Article
- Alzheimer disease: modeling an Aβ-centered biological network.Molecular psychiatry · 2016Article
- Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer's disease.Neuroscience and biobehavioral reviews · 2016Review
- Calsyntenin-3 molecular architecture and interaction with neurexin 1α.The Journal of biological chemistry · 2014Article
- Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.Molecular biology of the cell · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endocytosis of amyloid-β precursor protein (APP) is thought to represent the major source of substrate for the production of the amyloidogenic Aβ peptide by the β-secretase BACE1. The irreversible nature of proteolytic cleavage implies the existence of an efficient replenishment route for APP from its sites of synthesis to the cell surface. We recently found that APP exits the trans-Golgi network in intimate association with calsyntenin-1, a transmembrane cargo-docking protein for Kinesin-1-mediated vesicular transport. Here we characterized the function of calsyntenin-1 in neuronal APP transport using selective immunoisolation of intracellular trafficking organelles, immunocytochemistry, live-imaging, and RNAi. We found that APP is co-transported with calsyntenin-1 along axons to early endosomes in the central region of growth cones in carriers that exclude the α-secretase ADAM10. Intriguingly, calsyntenin-1/APP organelles contained BACE1, suggesting premature cleavage of APP along its anterograde path. However, we found that APP contained in calsyntenin-1/APP organelles was stable. We further analyzed vesicular trafficking of APP in cultured hippocampal neurons, in which calsyntenin-1 was reduced by RNAi. We found a markedly increased co-localization of APP and ADAM10 in axons and growth cones, along with increased proteolytic processing of APP and Aβ secretion in these neurons. This suggested that the reduced capacity for calsyntenin-1-dependent APP transport resulted in mis-sorting of APP into additional axonal carriers and, therefore, the premature encounter of unprotected APP with its ectodomain proteases. In combination, our results characterize calsyntenin-1/APP organelles as carriers for sheltered anterograde axonal transport of APP.
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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.