Thomas C. Südhof
Encyclopedia
Thomas C. Südhof is a biochemist well-known for his study of synaptic transmission. Since 1986, Dr. Sudhof's research has elucidated many major proteins mediating presynaptic functions. In fact, Sudhof's work has laid the foundation for our current scientific understanding of vesicle
-mediated neurotransmitter
release, and his continuing work focuses on the specificity of synaptogenesis
and synaptic maintenance.
at the University of Texas Health Science Center (now the UT Southwestern Medical Center) in Dallas, Texas
under the supervision of Michael Stuart Brown
and Joseph L. Goldstein
.
During his postdoctoral fellowship, Südhof worked to describe the role of the LDL receptor in cholesterol metabolism, for which Brown and Goldstein were awarded the Nobel Prize in Physiology or Medicine
in 1985. Südhof finished his postdoctoral training in 1986 and was made an investigator of the Howard Hughes Medical Institute
. He was also given his own laboratory at UT Southwestern Medical Center where he focused on the presynaptic neuron for over 20 years.
In 2008, Südhof moved to Stanford University and is currently the Avram Goldstein Professor in the School of Medicine as well as a Professor of Molecular & Cellular Physiology
, Psychiatry
, and Neurology
. During his career, Südhof has defined himself as a clear leader in synaptic research, and his work remains on the frontiers of discovery to this day.
dependent hormone release from neuroendocrine cells for his doctoral thesis at the Max Planck Institute for Biophysical Chemistry
. Südhof described the structure and function of chromaffin cells which are responsible for the release of epinephrine
, norepinephrine
, and endorphins from the medulla
of the adrenal gland
. Innervated by sympathetic nervous system
, chromaffin cells are important in the initiation of the fight or flight
response of animals when exposed to threatening stimuli.
After completing his thesis in 1983, Südhof moved to UT Southwestern Medical Center for his postdoctoral training where he began researching in the department of molecular genetics
under the supervision of Joseph L. Goldstein
and Michael Stuart Brown
. While a postdoctoral fellow, Südhof cloned the gene for the low-density lipoprotein receptor and, soon after, was able to explain its transcriptional regulation by cholesterol. When LDL receptors, found concentrated in the liver, bind specific free blood cholesterol, low-density lipoprotein, they are internalized and recycled removing the cholesterol from circulation. This process is a primary source of blood cholesterol regulation and variations in its efficiency were shown to be present in familial hypercholesterolemia
. As a result of the discovery, LDL receptor function had also elucidated the principle of receptor-mediated endocytosis
—a now universally understood process in cell biology. Goldstein and Brown won the Nobel Prize in Physiology or Medicine for the discovery in 1985.
After finishing postdoctoral training, Thomas Südhof started his own laboratory at UT Southwestern in 1986. Briefly continuing work with Goldstein and Brown, Südhof helped identify a DNA element in the LDL gene that produced sterol
mediated end-product repression when inserted in a viral promoter. This domain, known as a sterol regulatory sequence, directly participates in the regulation of sterol biosynthesis. Sterols are a major class of biomolecule and critical for life. Important sterols in humans include cholesterol
and steroid hormones. Discovery of sterol regulatory elements and LDL receptor function led to the subsequent development of statin
derived cholesterol medications such as atorvastatin
(Lipitor)—the top-selling branded pharmaceutical drug in the world in 2008.
As he began working independently, what made Südhof’s research so unique was his focus on the presynaptic neuron. Until Südhof began his work, majority of neuroscience research was aimed at the postsynaptic neuron and its role in learning and memory. Indeed, Thomas Südhof is credited with discovering much of the machinery mediating neurotransmitter release and presynaptic pasticity in his 21 years at UT Southwestern. Südhof began with the discovery of synaptotagmins and their role in neurotransmitter release from the presynaptic neuron. Synaptotagmin, a transmembrane protein found in neurosecretory vesicles, functions as a calcium sensor triggering vesicle fusion and neurotransmitter release. Stimulation of a neuron results in an increase in intracellular calcium concentration. After binding calcium ion to a region in its cytosolic domain, vesicular synaptotagmin promotes quick or slow neurotransmitter release from the presynaptic neuron via interaction with regulatory and fusion related proteins such as members of the SNARE
complex. Südhof also discovered RIMs and Muncs (most notably Munc13 and Munc18), soluble proteins which aid in the fusion of neurotransmitter vesicles to the nerve cell membrane and play an important role in synaptic plasticity. In addition, Südhof’s research uncovered the role of many other proteins facilitating vesicle binding, fusion, and resultant neurotransmitter release from the presynaptic neuron, including members of the SNARE
complex: synaptobrevin
, in the vesicular membrane, syntaxin
, in the cell membrane, and SNAP-25
, which is tethered to the cytosolic side of the cell membrane via cysteine-linked palmitoyl chains and holds the complex of four helices together. Südhof was also responsible for elucidating the action of tetanus and botulinum toxins, which selectively cleave synaptobrevin and SNAP-25, respectively, inhibiting vesicle fusion with the presynaptic membrane.
More recently, Thomas Südhof’s work has focused on aspects of synaptogenesis and maintenance of the synaptic connection. Südhof discovered neurexins, present on presynaptic neurons, and neuroligins, present on postsynaptic neurons, that come together to form a physical protein bridge across the synapse. The diversity in types of neurexins and neuroligins allows for a variety of unique binding opportunities between neurons and impart a specificity to synaptic connections. In additional studies, Südhof identified mutations in these proteins as a factor in inherited autism
.
Thomas Südhof currently continues work on the presynaptic neuron and related topics in his laboratory at Stanford University. Yet to be determined is the mechanism by which neurexins and neuroligins locate each other to form the synapse, their transcriptional regulation, and control of their variability. Südhof’s research has not only given the scientific community a great understanding of the processes underlying synaptic transmission, but has also advanced medical knowledge of mechanisms behind poorly understood diseases such as Alzheimer’s, Schizophrenia, and Autism. He is currently working with a diverse group of researchers at the Howard Hughes Medical Institute
to develop mouse models for mutants of synaptic genes. The project aims to drastically advance our understanding of neurological disorders. He also serves on the Research Consortium of Cure Alzheimer's Fund
.
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
-mediated neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
release, and his continuing work focuses on the specificity of synaptogenesis
Synaptogenesis
Synaptogenesis is the formation of synapses. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development...
and synaptic maintenance.
Biography
A German native, Thomas C. Südhof was born in Göttingen in 1955. Südhof studied medicine at the University of Aachen, Harvard, and then the University of Göttingen where, in 1982, he obtained his M.D. The same year, Südhof finished work on his doctoral thesis, in which he described the structure and function of chromaffin cells, at the Max Planck Institute for Biophysical Chemistry in the lab of Viktor P. Whittaker. After a brief postdoctoral fellowship in Whittaker’s lab, Dr. Südhof moved to the United States in 1983, where he began postdoctoral training in the department of molecular geneticsMolecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
at the University of Texas Health Science Center (now the UT Southwestern Medical Center) in Dallas, Texas
Dallas, Texas
Dallas is the third-largest city in Texas and the ninth-largest in the United States. The Dallas-Fort Worth Metroplex is the largest metropolitan area in the South and fourth-largest metropolitan area in the United States...
under the supervision of Michael Stuart Brown
Michael Stuart Brown
Michael Stuart Brown is an American geneticist and Nobel Laureate. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of cholesterol metabolism.- Life and career :...
and Joseph L. Goldstein
Joseph L. Goldstein
Joseph L. Goldstein from Kingstree, South Carolina is a Nobel Prize winning biochemist and geneticist, and a pioneer in the study of cholesterol metabolism.-Biography:...
.
During his postdoctoral fellowship, Südhof worked to describe the role of the LDL receptor in cholesterol metabolism, for which Brown and Goldstein were awarded the Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
in 1985. Südhof finished his postdoctoral training in 1986 and was made an investigator of the Howard Hughes Medical Institute
Howard Hughes Medical Institute
Howard Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United...
. He was also given his own laboratory at UT Southwestern Medical Center where he focused on the presynaptic neuron for over 20 years.
In 2008, Südhof moved to Stanford University and is currently the Avram Goldstein Professor in the School of Medicine as well as a Professor of Molecular & Cellular Physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
, Psychiatry
Psychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
, and Neurology
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
. During his career, Südhof has defined himself as a clear leader in synaptic research, and his work remains on the frontiers of discovery to this day.
Research
Thomas C. Südhof lay the foundations for his scientific career studying the synapse early while studying the mechanisms of neurotransmitterNeurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
dependent hormone release from neuroendocrine cells for his doctoral thesis at the Max Planck Institute for Biophysical Chemistry
Max Planck Institute for Biophysical Chemistry
The Max Planck Institute for Biophysical Chemistry in Göttingen is a research institute of the Max Planck Society. Currently, 812 people work at the Institute, 353 of them are scientists....
. Südhof described the structure and function of chromaffin cells which are responsible for the release of epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, and endorphins from the medulla
Medulla
Medulla refers to the middle of something and derives from the Latin word for marrow. Its anatomical uses include:* Medulla oblongata, a part of the brain stem* Renal medulla, a part of the kidney* Adrenal medulla, a part of the adrenal gland...
of the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
. Innervated by sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
, chromaffin cells are important in the initiation of the fight or flight
Fight or Flight
Fight or Flight may refer to:* Fight-or-flight response, the biological response of animals to acute stress* "Fight or Flight!" , a song off the album Aneurythm by the American hard rock band Living Syndication...
response of animals when exposed to threatening stimuli.
After completing his thesis in 1983, Südhof moved to UT Southwestern Medical Center for his postdoctoral training where he began researching in the department of molecular genetics
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
under the supervision of Joseph L. Goldstein
Joseph L. Goldstein
Joseph L. Goldstein from Kingstree, South Carolina is a Nobel Prize winning biochemist and geneticist, and a pioneer in the study of cholesterol metabolism.-Biography:...
and Michael Stuart Brown
Michael Stuart Brown
Michael Stuart Brown is an American geneticist and Nobel Laureate. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of cholesterol metabolism.- Life and career :...
. While a postdoctoral fellow, Südhof cloned the gene for the low-density lipoprotein receptor and, soon after, was able to explain its transcriptional regulation by cholesterol. When LDL receptors, found concentrated in the liver, bind specific free blood cholesterol, low-density lipoprotein, they are internalized and recycled removing the cholesterol from circulation. This process is a primary source of blood cholesterol regulation and variations in its efficiency were shown to be present in familial hypercholesterolemia
Familial hypercholesterolemia
Familial hypercholesterolemia is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein , in the blood and early cardiovascular disease...
. As a result of the discovery, LDL receptor function had also elucidated the principle of receptor-mediated endocytosis
Receptor-mediated endocytosis
Receptor-mediated endocytosis , also called clathrin-dependent endocytosis, is a process by which cells internalize molecules by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized.-Process:After the binding of a...
—a now universally understood process in cell biology. Goldstein and Brown won the Nobel Prize in Physiology or Medicine for the discovery in 1985.
After finishing postdoctoral training, Thomas Südhof started his own laboratory at UT Southwestern in 1986. Briefly continuing work with Goldstein and Brown, Südhof helped identify a DNA element in the LDL gene that produced sterol
Sterol
Sterols, also known as steroid alcohols, are a subgroup of the steroids and an important class of organic molecules. They occur naturally in plants, animals, and fungi, with the most familiar type of animal sterol being cholesterol...
mediated end-product repression when inserted in a viral promoter. This domain, known as a sterol regulatory sequence, directly participates in the regulation of sterol biosynthesis. Sterols are a major class of biomolecule and critical for life. Important sterols in humans include cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
and steroid hormones. Discovery of sterol regulatory elements and LDL receptor function led to the subsequent development of statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
derived cholesterol medications such as atorvastatin
Atorvastatin
Atorvastatin , sold by Pfizer under the trade name Lipitor, is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms...
(Lipitor)—the top-selling branded pharmaceutical drug in the world in 2008.
As he began working independently, what made Südhof’s research so unique was his focus on the presynaptic neuron. Until Südhof began his work, majority of neuroscience research was aimed at the postsynaptic neuron and its role in learning and memory. Indeed, Thomas Südhof is credited with discovering much of the machinery mediating neurotransmitter release and presynaptic pasticity in his 21 years at UT Southwestern. Südhof began with the discovery of synaptotagmins and their role in neurotransmitter release from the presynaptic neuron. Synaptotagmin, a transmembrane protein found in neurosecretory vesicles, functions as a calcium sensor triggering vesicle fusion and neurotransmitter release. Stimulation of a neuron results in an increase in intracellular calcium concentration. After binding calcium ion to a region in its cytosolic domain, vesicular synaptotagmin promotes quick or slow neurotransmitter release from the presynaptic neuron via interaction with regulatory and fusion related proteins such as members of the SNARE
Snare
Snare may refer to:* Snare trap, a kind of trap used for capturing animals* Snare drum* SNARE , a family of proteins involved in vesicle fusion* The Snares, a group of islands approximately 200 kilometres south of New Zealand...
complex. Südhof also discovered RIMs and Muncs (most notably Munc13 and Munc18), soluble proteins which aid in the fusion of neurotransmitter vesicles to the nerve cell membrane and play an important role in synaptic plasticity. In addition, Südhof’s research uncovered the role of many other proteins facilitating vesicle binding, fusion, and resultant neurotransmitter release from the presynaptic neuron, including members of the SNARE
Snare
Snare may refer to:* Snare trap, a kind of trap used for capturing animals* Snare drum* SNARE , a family of proteins involved in vesicle fusion* The Snares, a group of islands approximately 200 kilometres south of New Zealand...
complex: synaptobrevin
Synaptobrevin
Synaptobrevins are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton that are part of the vesicle-associated membrane protein family....
, in the vesicular membrane, syntaxin
Syntaxin
Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis.- Domains :Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain , and an N-terminal regulatory domain ....
, in the cell membrane, and SNAP-25
SNAP-25
Synaptosomal-associated protein 25 is a protein that in humans is encoded by the SNAP25 gene. The SNAP-25 protein is a component of the SNARE complex, which is proposed to account for the specificity of membrane fusion and to directly execute fusion by forming a tight complex that brings the...
, which is tethered to the cytosolic side of the cell membrane via cysteine-linked palmitoyl chains and holds the complex of four helices together. Südhof was also responsible for elucidating the action of tetanus and botulinum toxins, which selectively cleave synaptobrevin and SNAP-25, respectively, inhibiting vesicle fusion with the presynaptic membrane.
More recently, Thomas Südhof’s work has focused on aspects of synaptogenesis and maintenance of the synaptic connection. Südhof discovered neurexins, present on presynaptic neurons, and neuroligins, present on postsynaptic neurons, that come together to form a physical protein bridge across the synapse. The diversity in types of neurexins and neuroligins allows for a variety of unique binding opportunities between neurons and impart a specificity to synaptic connections. In additional studies, Südhof identified mutations in these proteins as a factor in inherited autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
.
Thomas Südhof currently continues work on the presynaptic neuron and related topics in his laboratory at Stanford University. Yet to be determined is the mechanism by which neurexins and neuroligins locate each other to form the synapse, their transcriptional regulation, and control of their variability. Südhof’s research has not only given the scientific community a great understanding of the processes underlying synaptic transmission, but has also advanced medical knowledge of mechanisms behind poorly understood diseases such as Alzheimer’s, Schizophrenia, and Autism. He is currently working with a diverse group of researchers at the Howard Hughes Medical Institute
Howard Hughes Medical Institute
Howard Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United...
to develop mouse models for mutants of synaptic genes. The project aims to drastically advance our understanding of neurological disorders. He also serves on the Research Consortium of Cure Alzheimer's Fund
Cure Alzheimer's Fund
Cure Alzheimer's Fund, a 'doing business as' name for the Alzheimer's Disease Research Foundation, is a 501 public charity established to provide funding for targeted research into the causes of Alzheimer’s disease.-Mission:...
.
Awards
- 1993 W. Alden Spencer Award from Columbia University (shared with Richard Scheller)
- 1994 Wilhelm Feldberg Award
- 1997 Roger Eckert Award Lecture, Göttingen
- 1997 U.S. National Academy Award in Molecular Biology (shared with Richard Scheller)
- 2002 Elected to the National Academy of Sciences of the U.S.A.
- 2004 MetLife Award (shared with Roberto Malinow)
- Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research
- 2004 Ulf von Euler Award Lecture, Karolinska Institute
- 2007 Elected to the Institute of Medicine
- 2008 Bernhard Katz Award, Biophysical Society (shared with Reinhard Jahn)
- 2008 Passano Foundation Award
- 2010 Kavli Prize (shared with Richard Scheller and James Rothman)
Key Papers
- Morris, S.J., Costello, M.J., Robertson, J.D., Südhof, T.C., Odenwald, W.F., and Haynes, D.H. (1983) Chromaffin granules as a model for membrane fusion: implications for exocytosis. J. Autonom. Nerv. Syst. 7, 19-33.
- Südhof, T.C., Goldstein, J.L., Brown, M.S., and Russell, D.W. (1985) The LDL receptor gene: A mosaic of exons shared with different proteins. Science 228, 815-822.
- Ma, P.T.S., Gil, G., Südhof, T.C., Bilheimer, D.W., Goldstein, J.L., and Brown, M.S. (1986) Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits. Proc. Natl. Acad. Sci. U.S.A. 83, 8370-8374.
- Dawson, P.A., Hofmann, S.L., Van Der Westhuyzen, D.R., Südhof, T.C., Brown, M.S., and Goldstein, J.L. (1988) Sterol-dependent repression of low density lipoprotein receptor promoter mediated by 16-base pair sequence adjacent to binding site for transcription factor SP1. J. Biol. Chem. 263, 3372-3379.
- Südhof, T.C. (1990) The structure of the human synapsin I gene and protein. J. Biol. Chem. 265, 7849-7852.
- Archer, B.T., III, Özcelik, T., Jahn, R., Francke, U., and Südhof, T.C. (1990) Structures and chromosomal localizations of two human genes encoding synaptobrevins 1 and 2. J. Biol. Chem. 265, 17267-17273.
- Perin, M.S., Johnston, P.A., Özcelik, T., Jahn, R., Francke, U., and Südhof, T.C. (1991) Structural and functional conservation of synaptotagmin (p65) in Drosophila and humans. J. Biol. Chem. 266, 615-622.
- Brose, N., Petrenko, A.G., Südhof, T.C., and Jahn, R. (1992) Synaptotagmin: A Ca2+ sensor on the synaptic vesicle surface. Science 256, 1021-1025.
- Ushkaryov, Y.A., Petrenko, A.G., Geppert, M., and Südhof, T.C. (1992) Neurexins: Synaptic cell surface proteins related to the α-latrotoxin receptor and laminin. Science 257, 50-56.
- Link, E., Edelmann, L., Chow, J.H., Binz, T., Yamasaki, S., Eisel, U., Baumert, M., Südhof, T.C., Niemann, H., and Jahn, R. (1992) Tetanus toxin action: Inhibition of neurotransmitter release linked to synaptobrevin proteolysis. Biochem. Biophys. Res. Comm. 189, 1017-1023.
- Blasi, J., Chapman, E.R., Link, E., Binz, T., Yamasaki, S., De Camilli, P., Südhof, T.C., Niemann, H., and Jahn, R. (1993) Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature 365, 160-163.
- Rosahl, T.W., Geppert, M., Spillane, D., Herz, J., Hammer, R.E., Malenka, R.C., and Südhof, T.C. (1993) Short term synaptic plasticity is altered in mice lacking synapsin I. Cell 75, 661-670.
- Geppert, M., Bolshakov, V.Y., Siegelbaum, S.A., Takei, K., De Camilli, P., Hammer, R.E., and Südhof, T.C. (1994) The role of Rab3A in neurotransmitter release. Nature 369, 493-497.
- Geppert, M., Goda, Y., Hammer, R.E., Li, C., Rosahl, T.W., Stevens, C.F., and Südhof, T.C. (1994) Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse. Cell 79, 717-727.
- McMahon, H.T., and Südhof, T.C. (1995) Synaptic core complex of synaptobrevin, syntaxin, and SNAPS forms high affinity α-SNAP binding site. J. Biol. Chem. 270, 2213-2217.
- Ullrich, B., Ushkaryov, Y.A., and Südhof, T.C. (1995) Cartography of neurexins: More than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron 14, 497-507.
- Ichtchenko, K., Hata, Y., Nguyen, T., Ullrich, B., Missler, M., Moomaw, C., and Südhof, T.C. (1995) Neuroligin 1: A splice-site specific ligand for ß-neurexins. Cell 81, 435-443.
- Shao, X., Li, C., Fernandez, I., Zhang, X., Südhof, T.C., and Rizo, J. (1997) Synaptotagmin-syntaxin interaction: the C2-domain as a Ca2+-dependent electrostatic switch. Neuron 18, 133-142.
- Nguyen, T., and Südhof, T.C. (1997) Binding properties of neuroligin 1 and neurexin 1ß reveal function as heterophilic cell adhesion molecules. J. Biol. Chem. 272, 26032-26039.
- Okamoto, M., and Südhof, T.C. (1997) Mints: Munc18-interacting proteins in synaptic vesicle exocytosis. J. Biol. Chem. 272, 31459-31464.
- Betz, A., Ashery, U., Rickmann, M., Augustin, I., Neher, E., Südhof, T.C., Rettig, J., and Brose, N. (1998) Munc13-1 is a presynaptic phorbol ester-receptor that stimulates neurotransmitter release. Neuron 21, 123-126.
- Wang, Y., Sugita, S., and Südhof, T.C. (2000) The RIM/NIM family of neuronal SH3-domain proteins: interactions with Rab3 and a new class of neuronal SH3-domain proteins. J. Biol. Chem. 275, 20033-20044.
- Lonart, G., and Südhof, T.C. (2000) Assembly of SNARE core complexes occurs prior to neurotransmitter release to set the readily-releasable pool of synaptic vesicles. J. Biol. Chem. 275, 27703-27707.
- Schoch, S., Castillo, P.E., Jo, T., Mukherjee, K., Geppert, M., Wang, Y., Schmitz, F., Malenka, R.C., and Südhof, T.C. (2002) RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature 415, 321-326.
- Chen, X, Tomchick, D.R., Kovrigin, E., Arac, D., Machius, M., Südhof, T.C., and Rizo, J. (2002) Three-dimensional structure of the complexin/SNARE complex. Neuron 33, 397-409.
- Schlüter, O.M., Fornai, F., Alessandri, M.G., Takamori, S., Geppert, M., Jahn, R., and Südhof, T.C. (2003) Role of α-Synuclein in MPTP-Induced Parkinsonism in Mice. Neuroscience 118, 985-1002.
- Matos, M.F., Chen, X., Rizo, J., and Südhof, T.C. (2003) Evidence for SNARE zippering during Ca2+-triggered exocytosis in PC12 cells. Neuropharmacology 45, 777-786.
- Powell, C.M., Schoch, S., Monteggia, L., Barrot, M., Matos, M.F., Südhof, T.C., and Nestler, E.J. (2004) The Presynaptic Active Zone Protein RIM1α is Critical for Normal Associative Learning. Neuron 42, 143-153.
- Dulubova, I., Ho, A., Südhof, T.C., and Rizo, J. (2004) Three-Dimensional Structure of an Independently Folded Extracellular Domain of Human Amyloid-β Precursor Protein. Biochemistry 43, 9583-9588.
- Chubykin, A.A., Liu, X., Comoletti, D., Tsigelny, I., Taylor, P., and Südhof, T.C. (2005) Dissection of Synapse Induction by Neuroligins: Effect of a Neuroligin Mutation Associated with Autism. J. Biol. Chem. 280, 22365-22374.
- Borisovska, M., Zhao, Y., Tsytsyura, Y., Glyvuk, N., Takamori, S., Matti, U., Rettig, J., Südhof, T.C., and Bruns, D. (2005) v-SNAREs control exocytosis of vesicles from priming to fusion. EMBO J. 24, 2114-2126.
- Pang, Z.P., Shin, O-H., Meyer, A.C., Rosenmund, C., and Südhof, T.C. (2006) A gain-of-function mutation in synaptotagmin-1 reveals a critical role of Ca2+-dependent SNARE-complex binding in synaptic exocytosis. J. Neurosci. 26, 12556-12565.
- Tabuchi, K., Blundell, J., Etherton, M.R., Hammer, R.E., Liu, X., Powell, C.M., and Südhof, T.C. (2007) A Neuroligin-3 Mutation Implicated in Autism Increases Inhibitory Synaptic Transmission in Mice. Science 318, 71-76.
- Ho, A., Liu, X., and Südhof, T.C. (2008) Deletion of Mint proteins decreases amyloid production in transgenic mouse models of Alzheimer’s disease. J. Neurosci. 28, 14392-14400.
- Blundell, J., Tabuchi, K., Bolliger, M.F., Blaiss, C.A., Brose, N., Liu, X., Südhof, T.C., and Powell, C.M. (2008) Increased Anxiety-like Behavior in Mice Lacking the Inhibitory Synapse Cell Adhesion Molecule Neuroligin 2. Genes Brain Behav., in press.
- Ko, J., Fuccillo, M. V., Malenka, R. C., and Südhof, T.C. (2009) LRRTM2 Functions as a Neurexin Ligand in Promoting Excitatory Synapse Formation. Neuron 64: 791-798.