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Accumulating evidence indicates that the lysosomal Ragulator complex is essential for full activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal mTORC1 activation has been implicated in several developmental neurological disorders, including Angelman syndrome (AS), which is caused by maternal deficiency of the ubiquitin E3 ligase UBE3A. Here we report that Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity. p18 knockdown in hippocampal CA1 neurons of AS mice reduces elevated mTORC1 activity and improves dendritic spine maturation, long-term potentiation (LTP), as well as learning performance. Our results indicate that Ube3a-mediated regulation of p18 and subsequent mTORC1 signaling is critical for typical synaptic plasticity, dendritic spine development, and learning and memory.
Pubmed ID: 30020076 RIS Download
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Software tool that detects peaks of any type, any shape, any direction, and any size for neuroscientists who are studying spontaneous activities. Allows detection of virtually any kind of peaks including spontaneous miniature synaptic currents and potentials, action potential spikes, calcium imaging peaks, amperometric peaks, ECG peaks etc. It includes the complex and multiple peak detection algorithm. Has post-detection analyses including essential plots and statistical parameters. Group Analysis provides specialized and detailed analysis options for action potentials, decay fitting, fEPSP/population spikes, amperometry, etc.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsA video-based system to detect animal movement in fear conditioning experiments, as well as movements in learned helplessness experiments. FreezeFrame can detect animal movements (as small as 1mm) and actions, including grooming, sniffing, turning, and rearing. It can also collect and process data for learned helplessness experiments, such as Tail Suspension and the Porsolt Forced Swim Test. This software can monitor animals for up to 15 times per second.
View all literature mentionsMus musculus with name B6.129S7-Ube3atm1Alb/J from IMSR.
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets Phospho-p70 S6 Kinase (Thr389)
View all literature mentionsThis monoclonal targets Mono- and polyubiquitinylated conjugates mAb (FK2)
View all literature mentionsThis polyclonal targets Rictor
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets E6AP
View all literature mentionsThis monoclonal targets RagC (D31G9) XP Rabbit mAb
View all literature mentionsThis polyclonal targets p70 S6 Kinase
View all literature mentionsThis monoclonal targets Raptor clone 1H6.2
View all literature mentionsThis polyclonal targets Phospho-S6 Ribosomal Protein (Ser240/244)
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets RagB (D18F3) Rabbit mAb
View all literature mentionsThis monoclonal targets 4E-BP1 (53H11) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-4E-BP1 (Ser65)
View all literature mentionsThis monoclonal targets RagA (D8B5) Rabbit mAb
View all literature mentionsThis monoclonal targets LAMTOR3/MAPKSP1 (D38G5) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-PKC (pan) (βII Ser660)
View all literature mentionsThis monoclonal targets LAMTOR2/ROBLD3 (D7C10) Rabbit mAb
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein
View all literature mentionsThis polyclonal targets Phospho-mTOR (Ser2448)
View all literature mentionsThis unknown targets mTOR
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis monoclonal targets LAMP1
View all literature mentionsThis unknown targets GFP
View all literature mentionsThis monoclonal targets COX IV (3E11) Rabbit mAb
View all literature mentionsThis monoclonal targets CA10
View all literature mentionsThis monoclonal targets LAMP2
View all literature mentionsThis monoclonal targets PSD-95
View all literature mentionsThis polyclonal targets ANTI-LAMTOR1 antibody produced in rabbit
View all literature mentionsThis monoclonal targets LAMTOR1/C11orf59 (D11H6) XP Rabbit mAb
View all literature mentionsCell line COS-1 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis unknown targets GFP
View all literature mentionsThis monoclonal targets COX IV (3E11) Rabbit mAb
View all literature mentionsThis monoclonal targets CA10
View all literature mentionsThis monoclonal targets PSD-95
View all literature mentionsThis polyclonal targets Rictor
View all literature mentionsThis monoclonal targets Raptor clone 1H6.2
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets 4E-BP1 (53H11) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-4E-BP1 (Ser65)
View all literature mentionsThis polyclonal targets Phospho-PKC (pan) (βII Ser660)
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein
View all literature mentionsThis polyclonal targets Phospho-S6 Ribosomal Protein (Ser240/244)
View all literature mentionsThis polyclonal targets p70 S6 Kinase
View all literature mentionsThis polyclonal targets Phospho-p70 S6 Kinase (Thr389)
View all literature mentionsThis unknown targets mTOR
View all literature mentionsThis polyclonal targets Phospho-mTOR (Ser2448)
View all literature mentionsThis monoclonal targets LAMP1
View all literature mentionsThis monoclonal targets LAMP2
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Mono- and polyubiquitinylated conjugates mAb (FK2)
View all literature mentionsThis monoclonal targets RagC (D31G9) XP Rabbit mAb
View all literature mentionsThis monoclonal targets RagB (D18F3) Rabbit mAb
View all literature mentionsThis monoclonal targets RagA (D8B5) Rabbit mAb
View all literature mentionsThis monoclonal targets LAMTOR3/MAPKSP1 (D38G5) Rabbit mAb
View all literature mentionsThis monoclonal targets LAMTOR2/ROBLD3 (D7C10) Rabbit mAb
View all literature mentionsThis monoclonal targets E6AP
View all literature mentionsCell line COS-1 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
View all literature mentionsThis polyclonal targets ANTI-LAMTOR1 antibody produced in rabbit
View all literature mentionsThis monoclonal targets LAMTOR1/C11orf59 (D11H6) XP Rabbit mAb
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