ArticleThe EMBO journal2019
Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Biallelic loss-of-function variants in DSCAM cause a neurodevelopmental syndrome with nystagmus and retinal dysfunction.HGG advances · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- The intracellular domain of the epilepsy protein PCDH19 regulates spine density in cortical neurons in vivo viaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- OMG! A proteomic determinant of neurodegenerative resiliency.Molecular neurodegeneration · 2026Article
- Future Directions for Studying the Potential of Mammalian Dscam in Autism Spectrum Disorder and Alzheimer's Disease: Insights from Dose Sensitivity.Molecular neurobiology · 2025Review
- Current insights into insect immune memory.eLife · 2025Review
- An in vivo screen identifies diverse domains that can act as force-dependent proteolytic switches for Notch activation.Science signaling · 2025Article
- Bayesian inference of genetic pleiotropy identifies drug targets and repurposable medicines for human complex diseases.medRxiv : the preprint server for health sciences · 2025Article
- Exploring perspectives of Dscam for cognitive deficits: a review of multifunction for regulating neural wiring in homeostasis.Frontiers in molecular neuroscience · 2025Review
- Distinct neuroprotective and anti-inflammatory effects of Kampo formulas ninjinyoeito and juzentaihoto in depression-like SAMP8 mice.Frontiers in pharmacology · 2025Article
- Endosomal Trafficking Bypassed by the RAB5B-CD109 Interplay Promotes Axonogenesis in KRAS-Mutant Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Increased endothelial sclerostin caused by elevated DSCAM mediates multiple trisomy 21 phenotypes.The Journal of clinical investigation · 2024Article
- Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons.Nature communications · 2024Article
- Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation.Nature communications · 2024Article
- Deficiency in the cell-adhesion moleculeFrontiers in cell and developmental biology · 2023Article
- γ-secretase promotes Drosophila postsynaptic development through the cleavage of a Wnt receptor.Developmental cell · 2022Article
- DSCAM Deficiency Leads to Premature Spine Maturation and Autism-like Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives.Frontiers in cellular neuroscience · 2022Review
- To Stick or Not to Stick: The Multiple Roles of Cell Adhesion Molecules in Neural Circuit Assembly.Frontiers in neuroscience · 2022Review
- Insights Into the Properties, Biological Functions, and Regulation of USP21.Frontiers in pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
DSCAM and DSCAML1 are immunoglobulin and cell adhesion-type receptors serving important neurodevelopmental functions including control of axon growth, branching, neurite self-avoidance, and neuronal cell death. The signal transduction mechanisms or effectors of DSCAM receptors, however, remain poorly characterized. We used a human ORFeome library to perform a high-throughput screen in mammalian cells and identified novel cytoplasmic signaling effector candidates including the Down syndrome kinase Dyrk1a, STAT3, USP21, and SH2D2A. Unexpectedly, we also found that the intracellular domains (ICDs) of DSCAM and DSCAML1 specifically and directly interact with IPO5, a nuclear import protein of the importin beta family, via a conserved nuclear localization signal. The DSCAM ICD is released by γ-secretase-dependent cleavage, and both the DSCAM and DSCAML1 ICDs efficiently translocate to the nucleus. Furthermore, RNA sequencing confirms that expression of the DSCAM as well as the DSCAML1 ICDs alone can profoundly alter the expression of genes associated with neuronal differentiation and apoptosis, as well as synapse formation and function. Gain-of-function experiments using primary cortical neurons show that increasing the levels of either the DSCAM or the DSCAML1 ICD leads to an impairment of neurite growth. Strikingly, increased expression of either full-length DSCAM or the DSCAM ICD, but not the DSCAML1 ICD, significantly decreases synapse numbers in primary hippocampal neurons. Taken together, we identified a novel membrane-to-nucleus signaling mechanism by which DSCAM receptors can alter the expression of regulators of neuronal differentiation and synapse formation and function. Considering that chromosomal duplications lead to increased DSCAM expression in trisomy 21, our findings may help uncover novel mechanisms contributing to intellectual disability in Down syndrome.
Indexed as
Identifiers
What OpenQuestion holds
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.