ArticleBiological psychiatry2016
Receptor Tyrosine Kinase MET Interactome and Neurodevelopmental Disorder Partners at the Developing Synapse.
Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Comparative Single-Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices.Developmental neuroscience · 2025Article
- Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort.International journal of molecular sciences · 2024Article
- Structural and functional changes in drug-naïve benign childhood epilepsy with centrotemporal spikes and their associated gene expression profiles.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- NMDA Receptor and Its Emerging Role in Cancer.International journal of molecular sciences · 2023Review
- Alterations in the Proteome of Developing Neocortical Synaptosomes in the Absence of MET Signaling Revealed by Comparative Proteomics.Developmental neuroscience · 2023Article
- B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer.iScience · 2022Article
- Article
- Conditional knockout of MET receptor tyrosine kinase in cortical excitatory neurons leads to enhanced learning and memory in young adult mice but early cognitive decline in older adult mice.Neurobiology of learning and memory · 2021Article
- Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Developmental Connectivity and Molecular Phenotypes of Unique Cortical Projection Neurons that Express a Synapse-Associated Receptor Tyrosine Kinase.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Insulin receptor sensitization restores neocortical excitation/inhibition balance in a mouse model of autism.Molecular autism · 2018Article
- Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders.Nature neuroscience · 2017Article
- The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism.Biological psychiatry · 2017Review
- Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAtypical synapse development and plasticity are implicated in many neurodevelopmental disorders (NDDs). NDD-associated, high-confidence risk genes have been identified, yet little is known about functional relationships at the level of protein-protein interactions, which are the dominant molecular bases responsible for mediating circuit development.
methodsProteomics in three independent developing neocortical synaptosomal preparations identified putative interacting proteins of the ligand-activated MET receptor tyrosine kinase, an autism risk gene that mediates synapse development. The candidates were translated into interactome networks and analyzed bioinformatically. Additionally, three independent quantitative proximity ligation assays in cultured neurons and four independent immunoprecipitation analyses of synaptosomes validated protein interactions.
resultsApproximately 11% (8/72) of MET-interacting proteins, including SHANK3, SYNGAP1, and GRIN2B, are associated with NDDs. Proteins in the MET interactome were translated into a novel MET interactome network based on human protein-protein interaction databases. High-confidence genes from different NDD datasets that encode synaptosomal proteins were analyzed for being enriched in MET interactome proteins. This was found for autism but not schizophrenia, bipolar disorder, major depressive disorder, or attention-deficit/hyperactivity disorder. There is correlated gene expression between MET and its interactive partners in developing human temporal and visual neocortices but not with highly expressed genes that are not in the interactome. Proximity ligation assays and biochemical analyses demonstrate that MET-protein partner interactions are dynamically regulated by receptor activation.
conclusionsThe results provide a novel molecular framework for deciphering the functional relations of key regulators of synaptogenesis that contribute to both typical cortical development and to NDDs.
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