ArticleProceedings of the National Academy of Sciences of the United States of America2015
Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- A Four Amino Acid Intracellular Motif of VISTA Blocks Growth Receptor Signaling in Cancer Cells to Induce Tumor Suppression.Cancer research · 2025Article
- Sculptors of cerebellar fissures and their potential as therapeutic targets for cerebellar dysfunction.Frontiers in cellular neuroscience · 2025Review
- Sepsis Impairs Purkinje Cell Functions and Motor Behaviors Through Microglia Activation.Cerebellum (London, England) · 2024Article
- cAMP-EPAC-PKCε-RIM1α signaling regulates presynaptic long-term potentiation and motor learning.eLife · 2023Article
- Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation.Molecular brain · 2023Article
- Group 1 Metabotropic Glutamate Receptors in Neurological and Psychiatric Diseases: Mechanisms and Prospective.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Review
- Group I Metabotropic Glutamate Receptors and Interacting Partners: An Update.International journal of molecular sciences · 2022Review
- SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate.National science review · 2021Article
- Reducing the expression of the Numb adaptor protein in neurons increases the searching behavior ofmicroPublication biology · 2021Article
- Different roles of Numb-p72 and Numb-p65 on the trafficking of metabotropic glutamate receptor 5.Molecular biology reports · 2021Article
- Deletion ofFrontiers in cell and developmental biology · 2020Article
- Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations.Cells · 2019Review
- MEA6 Deficiency Impairs Cerebellar Development and Motor Performance by Tethering Protein Trafficking.Frontiers in cellular neuroscience · 2019Article
- Metabotropic glutamate receptor trafficking.Molecular and cellular neurosciences · 2018Review
- Celecoxib Ameliorates Seizure Susceptibility in Autosomal Dominant Lateral Temporal Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Decreased Anxiety-Related Behaviour but Apparently Unperturbed NUMB Function in Ligand of NUMB Protein-X (LNX) 1/2 Double Knockout Mice.Molecular neurobiology · 2017Article
- Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- APP Protein Family Signaling at the Synapse: Insights from Intracellular APP-Binding Proteins.Frontiers in molecular neuroscience · 2017Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Protein Numb, first identified as a cell-fate determinant in Drosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in clathrin-coated vesicles in vitro. Nevertheless, its function in mature neurons has not yet been elucidated. Here we show that cerebellar Purkinje cells (PCs) express high levels of Numb during adulthood and that conditional deletion of Numb in PCs is sufficient to impair motor coordination despite maintenance of a normal cerebellar cyto-architecture. Numb proved to be critical for internalization and recycling of metabotropic glutamate 1 receptor (mGlu1) in PCs. A significant decrease of mGlu1 and an inhibition of long-term depression at the parallel fiber-PC synapse were observed in conditional Numb knockout mice. Indeed, the trafficking of mGlu1 induced by agonists was inhibited significantly in these mutants, but the expression of ionotropic glutamate receptor subunits and of mGlu1-associated proteins was not affected by the loss of Numb. Moreover, transient and persistent forms of mGlu1 plasticity were robustly induced in mutant PCs, suggesting that they do not require mGlu1 trafficking. Together, our data demonstrate that Numb is a regulator for constitutive expression and dynamic transport of mGlu1.
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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.