ArticleThe Journal of cell biology2022
Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Phosphatidylinositol-3-phosphate-dependent Klp98A recruitment regulates endosomal flux underlying developmental synaptic remodeling via Rab4.Journal of cell science · 2026Article
- Transcriptomic identification and developmental mapping ofTurkish journal of biology = Turk biyoloji dergisi · 2026Article
- 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
- Synapsin III promotes neuronal-like transdifferentiation of glioblastoma stem cells by disrupting JAG1-Notch1 interaction.Neuro-oncology · 2025Article
- Genome-wide association reveals a locus in neuregulin 3 associated with gabapentin efficacy in women with chronic pelvic pain.iScience · 2024Article
- ER-PM Junctions on GABAergic Interneurons Are Organized by Neuregulin 2/VAP Interactions and Regulated by NMDA Receptors.International journal of molecular sciences · 2023Article
- Keeping the balance: Trade-offs between human brain evolution, autism, and schizophrenia.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Neuregulins (NRGs) are EGF-like ligands associated with cognitive disorders. Unprocessed proNRG3 is cleaved by BACE1 to generate the mature membrane-bound NRG3 ligand, but the subcellular site of proNRG3 cleavage, mechanisms underlying its transport into axons, and presynaptic accumulation remain unknown. Using an optogenetic proNRG3 cleavage reporter (LA143-NRG3), we investigate the spatial-temporal dynamics of NRG3 processing and sorting in neurons. In dark conditions, unprocessed LA143-NRG3 is retained in the trans-Golgi network but, upon photoactivation, is cleaved by BACE1 and released from the TGN. Mature NRG3 then emerges on the somatodendritic plasma membrane from where it is re-endocytosed and anterogradely transported on Rab4+ vesicles into axons via transcytosis. By contrast, the BACE1 substrate APP is sorted into axons on Rab11+ vesicles. Lastly, by a mechanism we denote "trans-synaptic retention," NRG3 accumulates at presynaptic terminals by stable interaction with its receptor ErbB4 on postsynaptic GABAergic interneurons. We propose that trans-synaptic retention may account for polarized expression of other neuronal transmembrane ligands and receptors.
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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.