ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Structural Similarities between Neuregulin 1-3 Isoforms Determine Their Subcellular Distribution and Signaling Mode in Central Neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Transcriptomic identification and developmental mapping ofTurkish journal of biology = Turk biyoloji dergisi · 2026Article
- Chronic Overexpression of Neuronal NRG1-III in Mice Causes Long-Term Detrimental Changes in Lower Motor Neurons, Neuromuscular Synapses and Motor Behaviour.International journal of molecular sciences · 2025Article
- Multiple Roles for Neuregulins and Their v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog Receptors in Neurodegenerative Disease Pathogenesis and Therapy.The American journal of pathology · 2025Review
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.The Journal of biological chemistry · 2025Article
- Diversification of dentate gyrus granule cell subtypes is regulated by Nrg1 nuclear back-signaling.Life science alliance · 2025Article
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.bioRxiv : the preprint server for biology · 2025Article
- Neuregulin1 Nuclear Signaling Influences Adult Neurogenesis and Regulates a Schizophrenia Susceptibility Gene Network within the Mouse Dentate Gyrus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Genome-wide association reveals a locus in neuregulin 3 associated with gabapentin efficacy in women with chronic pelvic pain.iScience · 2024Article
- Dynamic effects of ventral hippocampal NRG3/ERBB4 signaling on nicotine withdrawal-induced responses.Neuropharmacology · 2024Article
- Schizophrenia Animal Modeling with Epidermal Growth Factor and Its Homologs: Their Connections to the Inflammatory Pathway and the Dopamine System.Biomolecules · 2023Review
- ER-PM Junctions on GABAergic Interneurons Are Organized by Neuregulin 2/VAP Interactions and Regulated by NMDA Receptors.International journal of molecular sciences · 2023Article
- Toxic and Phenotypic Effects of AAV_Cre Used to Transduce Mesencephalic Dopaminergic Neurons.International journal of molecular sciences · 2022Article
- Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3.The Journal of cell biology · 2022Article
- Developmental, neurochemical, and behavioral analyses of ErbB4 Cyt-1 knockout mice.Journal of neurochemistry · 2022Article
- Keeping the balance: Trade-offs between human brain evolution, autism, and schizophrenia.Frontiers in genetics · 2022Review
- Growth Factors as Axon Guidance Molecules: Lessons FromFrontiers in neuroscience · 2021Review
- Subcellular sorting of neuregulins controls the assembly of excitatory-inhibitory cortical circuits.eLife · 2020Article
- Neuregulins 1, 2, and 3 Promote Early Neurite Outgrowth in ErbB4-Expressing Cortical GABAergic Interneurons.Molecular neurobiology · 2020Article
- Neuregulin and ErbB expression is regulated by development and sensory experience in mouse visual cortex.The Journal of comparative neurology · 2020Article
- On the Modulatory Roles of Neuregulins/ErbB Signaling on Synaptic Plasticity.International journal of molecular sciences · 2019Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters, and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases. Here we systematically investigated the subcellular distribution and processing of major NRG isoforms in rat hippocampal neurons. We show that NRG1 isotypes I and II, which like NRG2 are single-pass transmembrane proteins with an Ig-like domain, share the same subcellular distribution and ectodomain shedding properties. We furthermore show that NRG3, like CRD-NRG1, is a dual-pass transmembrane protein that harbors a second transmembrane domain near its amino terminus. Both NRG3 and CRD-NRG1 cluster on axons through juxtacrine interactions with ErbB4 present on GABAergic interneurons. Interestingly, although single-pass NRGs accumulate as unprocessed proforms, axonal puncta of CRD-NRG1 and NRG3 are comprised of processed protein. Mutations of CRD-NRG1 and NRG3 that render them resistant to BACE cleavage, as well as BACE inhibition, result in the loss of axonal puncta and in the accumulation of unprocessed proforms in neuronal soma. Together, these results define two groups of NRGs with distinct membrane topologies and fundamentally different targeting and processing properties in central neurons. The implications of this functional diversity for the regulation of neuronal processes by the NRG/ErbB pathway are discussed.
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