ArticleMolecular psychiatry2015
Calcyon stimulates neuregulin 1 maturation and signaling.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- The protein interactome of the Neuron Specific Gene family (NSG1-3).bioRxiv : the preprint server for biology · 2025Article
- Knockout of AMPA receptor binding protein Neuron-specific gene 2 (NSG2) enhances associative learning and cognitive flexibility.Molecular brain · 2024Article
- Knockout of AMPA receptor binding protein Neuron-Specific Gene 2 (NSG2) enhances associative learning and cognitive flexibility.Research square · 2024Article
- Synaptic plasticity in schizophrenia pathophysiology.IBRO neuroscience reports · 2023Article
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 2023Article
- Synaptic plasticity in schizophrenia pathophysiology.IBRO neuroscience reports · 2022Article
- Global loss of Neuron-specific gene 1 causes alterations in motor coordination, increased anxiety, and diurnal hyperactivity in male mice.Genes, brain, and behavior · 2022Article
- Neuregulin-1, a potential therapeutic target for cardiac repair.Frontiers in pharmacology · 2022Review
- Overexpression of neuregulin 1 in GABAergic interneurons results in reversible cortical disinhibition.Nature communications · 2021Article
- Comparative Study of ROCK1 and ROCK2 in Hippocampal Spine Formation and Synaptic Function.Neuroscience bulletin · 2019Article
- Dynein binds and stimulates axonal motility of the endosome adaptor and NEEP21 family member, calcyon.The international journal of biochemistry & cell biology · 2017Article
- Glutamate-dependent ectodomain shedding of neuregulin-1 type II precursors in rat forebrain neurons.PloS one · 2017Article
- Neurological dysfunctions associated with altered BACE1-dependent Neuregulin-1 signaling.Journal of neurochemistry · 2016Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuregulin1 (NRG1) is a single transmembrane protein that plays a critical role in neural development and synaptic plasticity. Both NRG1 and its receptor, ErbB4, are well-established risk genes of schizophrenia. The NRG1 ecto-domain (ED) binds and activates ErbB4 following proteolytic cleavage of pro-NRG1 precursor protein. Although several studies have addressed the function of NRG1 in brain, very little is known about the cleavage and shedding mechanism. Here we show that the neuronal vesicular protein calcyon is a potent activator and key determinant of NRG1 ED cleavage and shedding. Calcyon stimulates clathrin-mediated endocytosis and endosomal targeting; and its levels are elevated in postmortem brains of schizophrenics. Overexpression of calcyon stimulates NRG1 cleavage and signaling in vivo, and as a result, GABA transmission is enhanced in calcyon overexpressing mice. Conversely, NRG1 cleavage, ErbB4 activity and GABA transmission are decreased in calcyon null mice. Moreover, stimulation of NRG1 cleavage by calcyon was recapitulated in HEK 293 cells suggesting the mechanism involved is cell-autonomous. Finally, studies with site-specific mutants in calcyon and inhibitors for the major sheddases indicate that the stimulatory effects of calcyon on NRG1 cleavage and shedding depend on clathrin-mediated endocytosis, β-secretase 1, and interaction with clathrin adaptor proteins. Together these results identify a novel mechanism for NRG1 cleavage and shedding.
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