Thomas C Sudhof

Summary

Affiliation: Stanford University
Country: USA

Publications

  1. Hsu Y, Li J, Wu D, Sudhof T, Chen L. Synaptic retinoic acid receptor signaling mediates mTOR-dependent metaplasticity that controls hippocampal learning. Proc Natl Acad Sci U S A. 2019;: pubmed publisher
    ..Thus, our findings reveal an RARα- and mTOR-dependent mechanism by which homeostatic plasticity controls Hebbian plasticity and learning. ..
  2. Tanabe K, Ang C, Chanda S, Olmos V, Haag D, Levinson D, et al. Transdifferentiation of human adult peripheral blood T cells into neurons. Proc Natl Acad Sci U S A. 2018;115:6470-6475 pubmed publisher
    ..Thus, our method allows the generation of sufficient neurons for experimental interrogation from a defined, homogeneous, and readily accessible donor cell population. ..
  3. Ahlenius H, Chanda S, Webb A, Yousif I, Karmazin J, Prusiner S, et al. FoxO3 regulates neuronal reprogramming of cells from postnatal and aging mice. Proc Natl Acad Sci U S A. 2016;113:8514-9 pubmed publisher
    ..Hence, FoxO3 has a central role in the neuronal reprogramming susceptibility of cells, and the importance of FoxO3 appears to change during development. ..
  4. Voleti R, Tomchick D, Sudhof T, Rizo J. Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 C2A domain in asynchronous neurotransmitter release. Proc Natl Acad Sci U S A. 2017;114:E8518-E8527 pubmed publisher
    ..Viewed together, our results suggest that membrane affinity may be a key determinant of the functions of Syt C2 domains in neurotransmitter release. ..
  5. Luo F, Liu X, Sudhof T, Acuna C. Efficient stimulus-secretion coupling at ribbon synapses requires RIM-binding protein tethering of L-type Ca2+ channels. Proc Natl Acad Sci U S A. 2017;114:E8081-E8090 pubmed publisher
    ..These findings suggest that RBPs tether L-type Ca2+ channels to the active zones of ribbon synapses, thereby synchronizing vesicle exocytosis and promoting high-fidelity information transfer in retinal circuits. ..
  6. Lee S, Sharma M, S dhof T, Shen J. Synaptic function of nicastrin in hippocampal neurons. Proc Natl Acad Sci U S A. 2014;111:8973-8 pubmed publisher
    ..Together, these findings show that, similar to presenilins, nicastrin plays essential roles in the regulation of short- and long-term synaptic plasticity, highlighting the importance of ?-secretase in the function of mature synapses...
  7. Maxeiner S, Luo F, Tan A, Schmitz F, Südhof T. How to make a synaptic ribbon: RIBEYE deletion abolishes ribbons in retinal synapses and disrupts neurotransmitter release. EMBO J. 2016;35:1098-114 pubmed publisher
    ..Our results show that RIBEYE is essential for synaptic ribbons as such, and may organize presynaptic nano-domains that position release-ready synaptic vesicles adjacent to Ca(2+) channels. ..
  8. Liu C, Bickford L, Held R, Nyitrai H, Südhof T, Kaeser P. The active zone protein family ELKS supports Ca2+ influx at nerve terminals of inhibitory hippocampal neurons. J Neurosci. 2014;34:12289-303 pubmed publisher
    ..Our results reveal that ELKS is required for normal Ca(2+) influx at nerve terminals of inhibitory hippocampal neurons. ..
  9. Wu B, Wei S, Petersen N, Ali Y, Wang X, Bacaj T, et al. Synaptotagmin-7 phosphorylation mediates GLP-1-dependent potentiation of insulin secretion from β-cells. Proc Natl Acad Sci U S A. 2015;112:9996-10001 pubmed publisher
    ..Moreover, our data reveal, to our knowledge, the first physiological modulation of Ca(2+)-triggered exocytosis by direct phosphorylation of a synaptotagmin. ..

More Information

Publications41

  1. Sando R, Jiang X, Sudhof T. Latrophilin GPCRs direct synapse specificity by coincident binding of FLRTs and teneurins. Science. 2019;363: pubmed publisher
    ..Thus, postsynaptic latrophilins promote excitatory synapse formation by simultaneous binding of two unrelated presynaptic ligands, which is required for formation of synaptic inputs at specific dendritic localizations. ..
  2. Wu X, Morishita W, Riley A, Hale W, Sudhof T, Malenka R. Neuroligin-1 Signaling Controls LTP and NMDA Receptors by Distinct Molecular Pathways. Neuron. 2019;: pubmed publisher
    ..Our data suggest that neuroligin-1 performs two mechanistically distinct signaling functions and that neurolign-1-mediated trans-synaptic cell adhesion signaling critically regulates LTP. ..
  3. Sudhof T. Towards an Understanding of Synapse Formation. Neuron. 2018;100:276-293 pubmed publisher
    ..Among others, this hypothesis implies that synapse formation can be understood in terms of inter- and intracellular signaling, and that neuropsychiatric disorders involve an impairment in such signaling. ..
  4. Zhou M, Liu Z, Melin M, Ng Y, Xu W, Sudhof T. A central amygdala to zona incerta projection is required for acquisition and remote recall of conditioned fear memory. Nat Neurosci. 2018;: pubmed publisher
    ..Thus, the amygdala inhibitory input to parvalbumin-positive neurons in the zona incerta, a nucleus not previously implicated in fear memory, is an essential component of the fear memory circuitry. ..
  5. Seigneur E, Polepalli J, Sudhof T. Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular projections and contribute to different behavioral outputs. Proc Natl Acad Sci U S A. 2018;115:E10235-E10244 pubmed publisher
    ..Thus, Cbln2 and Cbln4 are expressed in distinct MHb neurons that contribute to different behaviors. ..
  6. Burré J, Sharma M, Südhof T. α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation. Proc Natl Acad Sci U S A. 2014;111:E4274-83 pubmed publisher
  7. Pak C, Danko T, Zhang Y, Aoto J, ANDERSON G, Maxeiner S, et al. Human Neuropsychiatric Disease Modeling using Conditional Deletion Reveals Synaptic Transmission Defects Caused by Heterozygous Mutations in NRXN1. Cell Stem Cell. 2015;17:316-28 pubmed publisher
  8. Li J, Shalev Benami M, Sando R, Jiang X, Kibrom A, Wang J, et al. Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse. Cell. 2018;173:735-748.e15 pubmed publisher
    ..These results highlight the unusual structural organization of TENs giving rise to their multifarious functions. ..
  9. Chanda S, Ang C, Davila J, Pak C, Mall M, Lee Q, et al. Generation of induced neuronal cells by the single reprogramming factor ASCL1. Stem Cell Reports. 2014;3:282-96 pubmed publisher
    ..Surprisingly, ASCL1-induced iN cells were predominantly excitatory, demonstrating that ASCL1 is permissive but alone not deterministic for the inhibitory neuronal lineage. ..
  10. Fuccillo M, Földy C, Gökce Ã, Rothwell P, Sun G, Malenka R, et al. Single-Cell mRNA Profiling Reveals Cell-Type-Specific Expression of Neurexin Isoforms. Neuron. 2015;87:326-40 pubmed publisher
  11. Seigneur E, Sudhof T. Genetic Ablation of All Cerebellins Reveals Synapse Organizer Functions in Multiple Regions Throughout the Brain. J Neurosci. 2018;38:4774-4790 pubmed publisher
    ..We also show that cerebellins are not initially required for synapse formation, but rather for specification and long-term synapse maintenance and demonstrate that all cerebellins, not just Cbln1, contribute to brain function. ..
  12. Sudhof T. The presynaptic active zone. Neuron. 2012;75:11-25 pubmed publisher
    ..Moreover, this complex mediates short- and long-term plasticity in response to bursts of action potentials, thus critically contributing to the computational power of a synapse. ..
  13. Huang Y, Zhou B, Wernig M, Sudhof T. ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and A? Secretion. Cell. 2017;168:427-441.e21 pubmed publisher
    ..Our data describe a novel signal transduction pathway in neurons whereby ApoE activates a non-canonical MAP kinase cascade that enhances APP transcription and amyloid-? synthesis. ..
  14. Sudhof T. Molecular Neuroscience in the 21st Century: A Personal Perspective. Neuron. 2017;96:536-541 pubmed publisher
  15. Anderson G, Maxeiner S, Sando R, Tsetsenis T, Malenka R, Südhof T. Postsynaptic adhesion GPCR latrophilin-2 mediates target recognition in entorhinal-hippocampal synapse assembly. J Cell Biol. 2017;216:3831-3846 pubmed publisher
    ..Thus, Lphn2 appears to control synapse numbers in the entorhinal cortex/CA1 region circuit by acting as a domain-specific postsynaptic target-recognition molecule. ..
  16. Luo F, Sudhof T. Synaptotagmin-7-Mediated Asynchronous Release Boosts High-Fidelity Synchronous Transmission at a Central Synapse. Neuron. 2017;94:826-839.e3 pubmed publisher
    ..Thus, asynchronous release surprisingly functions, at least at some synapses, to sustain high-fidelity neurotransmission driven by synchronous release during high-frequency stimulus trains. ..
  17. Chen L, Jiang M, Zhang B, Gokce O, Südhof T. Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins. Neuron. 2017;94:611-625.e4 pubmed publisher
    ..Thus, neurexins function primarily as context-dependent specifiers of synapses. ..
  18. Acuna C, Liu X, Sudhof T. How to Make an Active Zone: Unexpected Universal Functional Redundancy between RIMs and RIM-BPs. Neuron. 2016;91:792-807 pubmed publisher
    ..Thus, RBPs perform unexpectedly broad roles at the active zone that together with those of RIMs are essential for all active zone functions. ..
  19. Gokce O, Stanley G, Treutlein B, Neff N, Camp J, Malenka R, et al. Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq. Cell Rep. 2016;16:1126-1137 pubmed publisher
    ..Our findings suggest that functional diversity within a complex tissue arises from a small number of discrete cell types, which can exist in a continuous spectrum of functional states. ..
  20. Sudhof T. Calcium control of neurotransmitter release. Cold Spring Harb Perspect Biol. 2012;4:a011353 pubmed publisher
  21. Zhang B, Chen L, Liu X, Maxeiner S, Lee S, Gokce O, et al. Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of Distinct Classes of Synapses. Neuron. 2015;87:781-96 pubmed publisher
    ..Using systematic analyses of all neuroligins in a defined neural circuit, our data thus show that neuroligins differentially contribute to various Purkinje-cell synapses in the cerebellum in vivo. ..
  22. Liu Z, Chen Z, Shang C, Yan F, Shi Y, Zhang J, et al. IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning. Neuron. 2017;95:106-122.e5 pubmed publisher
    ..Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information. ..
  23. Sudhof T. Neurotransmitter release: the last millisecond in the life of a synaptic vesicle. Neuron. 2013;80:675-90 pubmed publisher
    ..This architecture allows direct flow of Ca(2+) ions from Ca(2+) channels to synaptotagmin, which then triggers fusion, thus mediating tight millisecond coupling of an action potential to neurotransmitter release. ..
  24. Yi F, Danko T, Botelho S, Patzke C, Pak C, Wernig M, et al. Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons. Science. 2016;352:aaf2669 pubmed publisher
    ..Our data suggest that SHANK3 mutations predispose to autism, at least partially, by inducing an Ih channelopathy that may be amenable to pharmacological intervention. ..
  25. Acuna C, Guo Q, Burré J, Sharma M, Sun J, Sudhof T. Microsecond dissection of neurotransmitter release: SNARE-complex assembly dictates speed and Ca²? sensitivity. Neuron. 2014;82:1088-100 pubmed publisher
  26. Acuna C, Liu X, Gonzalez A, Südhof T. RIM-BPs Mediate Tight Coupling of Action Potentials to Ca(2+)-Triggered Neurotransmitter Release. Neuron. 2015;87:1234-47 pubmed publisher
    ..Thus, RIM-BPs ensure optimal organization of the machinery for fast release in mammalian synapses without being a central component of the machinery itself. ..
  27. Anderson G, Aoto J, Tabuchi K, Földy C, Covy J, Yee A, et al. β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling. Cell. 2015;162:593-606 pubmed publisher
  28. Sudhof T, Rizo J. Synaptic vesicle exocytosis. Cold Spring Harb Perspect Biol. 2011;3: pubmed publisher
    ..The synaptic membrane-fusion machinery is controlled by synaptotagmin, and additionally regulated by a presynaptic protein matrix (the "active zone") that includes Munc13 and RIM proteins as central components. ..
  29. Sudhof T. Neuroligins and neurexins link synaptic function to cognitive disease. Nature. 2008;455:903-11 pubmed publisher
    ..In humans, alterations in genes encoding neurexins or neuroligins have recently been implicated in autism and other cognitive diseases, linking synaptic cell adhesion to cognition and its disorders. ..
  30. Sudhof T. Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits. Cell. 2017;171:745-769 pubmed publisher
  31. Rothwell P, Fuccillo M, Maxeiner S, Hayton S, Gokce O, Lim B, et al. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell. 2014;158:198-212 pubmed publisher
  32. Sudhof T, Rothman J. Membrane fusion: grappling with SNARE and SM proteins. Science. 2009;323:474-7 pubmed publisher