ArticleThe Journal of biological chemistry2010
Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Endosomal system genetics and autism spectrum disorders: A literature review.Neuroscience and biobehavioral reviews · 2016Pooled it
- Article
- Impairment of Group I Metabotropic Glutamate Receptors in the Dorsal Striatum of the R451C-Neuroligin 3 Mouse Model of Autism Spectrum Disorder.Journal of neurochemistry · 2025Article
- Perturbed synaptic adhesion molecules signaling in neurodevelopmental disorders: The impact of metal neurotoxicity.Ibrain · 2025Review
- Article
- Identification of proteotoxic and proteoprotective bacteria that non-specifically affect proteins associated with neurodegenerative diseases.bioRxiv : the preprint server for biology · 2023Article
- Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3.iScience · 2022Article
- Neuroligin-3: A Circuit-Specific Synapse Organizer That Shapes Normal Function and Autism Spectrum Disorder-Associated Dysfunction.Frontiers in molecular neuroscience · 2021Review
- Kirrel3-Mediated Synapse Formation Is Attenuated by Disease-Associated Missense Variants.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y.Neuron · 2020Article
- Functional significance of rare neuroligin 1 variants found in autism.PLoS genetics · 2017Article
- Proteolytic cleavage is required for functional neuroligin 2 maturation and trafficking in Drosophila.Journal of molecular cell biology · 2017Article
- Unbalance between Excitation and Inhibition in Phenylketonuria, a Genetic Metabolic Disease Associated with Autism.International journal of molecular sciences · 2017Article
- Autism-associated R451C mutation in neuroligin3 leads to activation of the unfolded protein response in a PC12 Tet-On inducible system.The Biochemical journal · 2016Article
- Slitrk Missense Mutations Associated with Neuropsychiatric Disorders Distinctively Impair Slitrk Trafficking and Synapse Formation.Frontiers in molecular neuroscience · 2016Article
- PKMζ, but not PKCλ, is rapidly synthesized and degraded at the neuronal synapse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Ubiquitin-Proteasome System in Neurodegenerative Disorders.Journal of drug metabolism & toxicology · 2015Article
- Cholinesterase confabs and cousins: approaching forty years.Chemico-biological interactions · 2013Article
- In vivo quantitative proteomics of somatosensory cortical synapses shows which protein levels are modulated by sensory deprivation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Congenital hypothyroidism mutations affect common folding and trafficking in the α/β-hydrolase fold proteins.The FEBS journal · 2012Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite great functional diversity, characterization of the alpha/beta-hydrolase fold proteins that encompass a superfamily of hydrolases, heterophilic adhesion proteins, and chaperone domains reveals a common structural motif. By incorporating the R451C mutation found in neuroligin (NLGN) and associated with autism and the thyroglobulin G2320R (G221R in NLGN) mutation responsible for congenital hypothyroidism into NLGN3, we show that mutations in the alpha/beta-hydrolase fold domain influence folding and biosynthetic processing of neuroligin3 as determined by in vitro susceptibility to proteases, glycosylation processing, turnover, and processing rates. We also show altered interactions of the mutant proteins with chaperones in the endoplasmic reticulum and arrest of transport along the secretory pathway with diversion to the proteasome. Time-controlled expression of a fluorescently tagged neuroligin in hippocampal neurons shows that these mutations compromise neuronal trafficking of the protein, with the R451C mutation reducing and the G221R mutation virtually abolishing the export of NLGN3 from the soma to the dendritic spines. Although the R451C mutation causes a local folding defect, the G221R mutation appears responsible for more global misfolding of the protein, reflecting their sequence positions in the structure of the protein. Our results suggest that disease-related mutations in the alpha/beta-hydrolase fold domain share common trafficking deficiencies yet lead to discrete congenital disorders of differing severity in the endocrine and nervous systems.
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