ArticleMolecular neurodegeneration2014
BACE1 activity regulates cell surface contactin-2 levels.
Article in Molecular neurodegeneration, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Associations between cerebrospinal fluid markers and cognition in ageing and dementia: A systematic review.The European journal of neuroscience · 2022Pooled it
- Contactin proteins in cerebrospinal fluid show different alterations in dementias.Journal of neurology · 2024Article
- The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer's Disease Reveals New Insights for AD Study.International journal of molecular sciences · 2023Article
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- β-Secretase BACE1 Is Required for Normal Cochlear Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency.Nutrients · 2019Article
- High-throughput epitope profiling of antibodies in the plasma of Alzheimer's disease patients using random peptide microarrays.Scientific reports · 2019Article
- Review
- Contactins in the central nervous system: role in health and disease.Neural regeneration research · 2019Review
- Click Chemistry-mediated Biotinylation Reveals a Function for the Protease BACE1 in Modulating the Neuronal Surface Glycoproteome.Molecular & cellular proteomics : MCP · 2018Article
- Contactin-2, a synaptic and axonal protein, is reduced in cerebrospinal fluid and brain tissue in Alzheimer's disease.Alzheimer's research & therapy · 2018Article
- Expression of Gas1 in Mouse Brain: Release and Role in Neuronal Differentiation.Cellular and molecular neurobiology · 2018Article
- β-Secretase BACE1 Promotes Surface Expression and Function of Kv3.4 at Hippocampal Mossy Fiber Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Beta secretase activity in peripheral nerve regeneration.Neural regeneration research · 2017Review
- Contactin-2/TAG-1, active on the front line for three decades.Cell adhesion & migration · 2017Article
- Tripchlorolide Attenuates β-amyloid Generation via Suppressing PPARγ-Regulated BACE1 Activity in N2a/APP695 Cells.Molecular neurobiology · 2016Article
- Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons.Molecular neurodegeneration · 2016Article
- Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer's disease.Neuroscience and biobehavioral reviews · 2016Review
- Neurological dysfunctions associated with altered BACE1-dependent Neuregulin-1 signaling.Journal of neurochemistry · 2016Review
- Regulating Axonal Responses to Injury: The Intersection between Signaling Pathways Involved in Axon Myelination and The Inhibition of Axon Regeneration.Frontiers in molecular neuroscience · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlthough BACE1 is a major therapeutic target for Alzheimer's disease (AD), potential side effects of BACE1 inhibition are not well characterized. BACE1 cleaves over 60 putative substrates, however the majority of these cleavages have not been characterized. Here we investigated BACE1-mediated cleavage of human contactin-2, a GPI-anchored cell adhesion molecule.
resultsOur initial protein sequence analysis showed that contactin-2 harbors a strong putative BACE1 cleavage site close to its GPI membrane linker domain. When we overexpressed BACE1 in CHO cells stably transfected with human contactin-2, we found increased release of soluble contactin-2 in the conditioned media. Conversely, pharmacological inhibition of BACE1 in CHO cells expressing human contactin-2 and mouse primary neurons decreased soluble contactin-2 secretion. The BACE1 cleavage site mutation 1008MM/AA dramatically impaired soluble contactin-2 release. We then asked whether contactin-2 release induced by BACE1 expression would concomitantly decrease cell surface levels of contactin-2. Using immunofluorescence and surface-biotinylation assays, we showed that BACE1 activity tightly regulates contactin-2 surface levels in CHO cells as well as in mouse primary neurons. Finally, contactin-2 levels were decreased in Alzheimer's disease brain samples correlating inversely with elevated BACE1 levels in the same samples.
conclusionOur results clearly demonstrate that mouse and human contactin-2 are physiological substrates for BACE1. BACE1-mediated contactin-2 cleavage tightly regulates the surface expression of contactin-2 in neuronal cells. Given the role of contactin-2 in cell adhesion, neurite outgrowth and axon guidance, our data suggest that BACE1 may play an important role in these physiological processes by regulating contactin-2 surface levels.
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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.