Scott Soderling

Positions:

Professor in Cell Biology

Cell Biology
School of Medicine

Interim Chair, Department of Cell Biology

Cell Biology
School of Medicine

Professor of Neurobiology

Neurobiology
School of Medicine

Faculty Network Member of the Duke Institute for Brain Sciences

Duke Institute for Brain Sciences
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1999

University of Washington

Postdoctoral Fellow, Hhmi

Oregon Health and Science University

Grants:

How Does Huntingtin Control Synaptic Development?

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Co-Mentor
Start Date
End Date

The effects of Nlrp12 and IL-1b in inflammatory disorders

Administered By
Medicine, Cardiology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Control of cell fate by progenitor mitosis length and microcephaly-linked genes during cortical development

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Co-Sponsor
Start Date
End Date

Interrogating the role of the novel synaptic protein Rogdi in GABAergic inhibition and epilepsy

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Analysis of Inhibitory Synaptic Proteins Associated with Brain Disorders

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Plug-and-Play Protein Modification Using Homology-Independent Universal Genome Engineering.

Analysis of endogenous protein localization, function, and dynamics is fundamental to the study of all cells, including the diversity of cell types in the brain. However, current approaches are often low throughput and resource intensive. Here, we describe a CRISPR-Cas9-based homology-independent universal genome engineering (HiUGE) method for endogenous protein manipulation that is straightforward, scalable, and highly flexible in terms of genomic target and application. HiUGE employs adeno-associated virus (AAV) vectors of autonomous insertional sequences (payloads) encoding diverse functional modifications that can integrate into virtually any genomic target loci specified by easily assembled gene-specific guide-RNA (GS-gRNA) vectors. We demonstrate that universal HiUGE donors enable rapid alterations of proteins in vitro or in vivo for protein labeling and dynamic visualization, neural-circuit-specific protein modification, subcellular rerouting and sequestration, and truncation-based structure-function analysis. Thus, the "plug-and-play" nature of HiUGE enables high-throughput and modular analysis of mechanisms driving protein functions in cellular neurobiology.
Authors
Gao, Y; Hisey, E; Bradshaw, TWA; Erata, E; Brown, WE; Courtland, JL; Uezu, A; Xiang, Y; Diao, Y; Soderling, SH
MLA Citation
Gao, Yudong, et al. “Plug-and-Play Protein Modification Using Homology-Independent Universal Genome Engineering..” Neuron, vol. 103, no. 4, Aug. 2019, pp. 583-597.e8. Pubmed, doi:10.1016/j.neuron.2019.05.047.
URI
https://scholars.duke.edu/individual/pub1395888
PMID
31272828
Source
pubmed
Published In
Neuron
Volume
103
Published Date
Start Page
583
End Page
597.e8
DOI
10.1016/j.neuron.2019.05.047

Identification of an elaborate complex mediating postsynaptic inhibition.

Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. The composition of the inhibitory postsynapse and the mechanistic basis of its regulation, however, remain poorly understood. We used an in vivo chemico-genetic proximity-labeling approach to discover inhibitory postsynaptic proteins. Quantitative mass spectrometry not only recapitulated known inhibitory postsynaptic proteins but also revealed a large network of new proteins, many of which are either implicated in neurodevelopmental disorders or are of unknown function. Clustered regularly interspaced short palindromic repeats (CRISPR) depletion of one of these previously uncharacterized proteins, InSyn1, led to decreased postsynaptic inhibitory sites, reduced the frequency of miniature inhibitory currents, and increased excitability in the hippocampus. Our findings uncover a rich and functionally diverse assemblage of previously unknown proteins that regulate postsynaptic inhibition and might contribute to developmental brain disorders.
Authors
Uezu, A; Kanak, DJ; Bradshaw, TWA; Soderblom, EJ; Catavero, CM; Burette, AC; Weinberg, RJ; Soderling, SH
MLA Citation
Uezu, Akiyoshi, et al. “Identification of an elaborate complex mediating postsynaptic inhibition..” Science, vol. 353, no. 6304, Sept. 2016, pp. 1123–29. Pubmed, doi:10.1126/science.aag0821.
URI
https://scholars.duke.edu/individual/pub1145755
PMID
27609886
Source
pubmed
Published In
Science
Volume
353
Published Date
Start Page
1123
End Page
1129
DOI
10.1126/science.aag0821

Disruption of wave-associated Rac GTPase-activating protein (Wrp) leads to abnormal adult neural progenitor migration associated with hydrocephalus.

Hydrocephalus is the most common developmental disability and leading cause of brain surgery for children. Current treatments are limited to surgical intervention, as the factors that contribute to the initiation of hydrocephalus are poorly understood. Here, we describe the development of obstructive hydrocephalus in mice that are null for Wrp (Srgap3). Wrp is highly expressed in the ventricular stem cell niche, and it is a gene required for cytoskeletal organization and is associated with syndromic and psychiatric disorders in humans. During the postnatal period of progenitor cell expansion and ventricular wall remodeling, loss of Wrp results in the abnormal migration of lineage-tagged cells from the ventricular region into the corpus callosum. Within this region, mutant progenitors appear to give rise to abnormal astroglial cells and induce periventricular lesions and hemorrhage that leads to cerebral aqueductal occlusion. These results indicate that periventricular abnormalities arising from abnormal migration from the ventricular niche can be an initiating cause of noncommunicating hydrocephalus.
Authors
Kim, IH; Carlson, BR; Heindel, CC; Kim, H; Soderling, SH
MLA Citation
Kim, Il Hwan, et al. “Disruption of wave-associated Rac GTPase-activating protein (Wrp) leads to abnormal adult neural progenitor migration associated with hydrocephalus..” J Biol Chem, vol. 287, no. 46, Nov. 2012, pp. 39263–74. Pubmed, doi:10.1074/jbc.M112.398834.
URI
https://scholars.duke.edu/individual/pub799367
PMID
23007397
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
287
Published Date
Start Page
39263
End Page
39274
DOI
10.1074/jbc.M112.398834

The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling.

WAVE-1, which is also known as Scar, is a scaffolding protein that directs actin reorganization by relaying signals from the GTPase Rac to the Arp2/3 complex. Although the molecular details of WAVE activation by Rac have been described, the mechanisms by which these signals are terminated remain unknown. Here we have used tandem mass spectrometry to identify previously unknown components of the WAVE signalling network including WRP, a Rac-selective GTPase-activating protein. WRP binds directly to WAVE-1 through its Src homology domain 3 and specifically inhibits Rac function in vivo. Thus, we propose that WRP is a binding partner of WAVE-1 that functions as a signal termination factor for Rac.
Authors
Soderling, SH; Binns, KL; Wayman, GA; Davee, SM; Ong, SH; Pawson, T; Scott, JD
MLA Citation
Soderling, Scott H., et al. “The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling..” Nat Cell Biol, vol. 4, no. 12, Dec. 2002, pp. 970–75. Pubmed, doi:10.1038/ncb886.
URI
https://scholars.duke.edu/individual/pub799380
PMID
12447388
Source
pubmed
Published In
Nature Cell Biology
Volume
4
Published Date
Start Page
970
End Page
975
DOI
10.1038/ncb886

A GABAergic nigrotectal pathway for coordination of drinking behavior.

The contribution of basal ganglia outputs to consummatory behavior remains poorly understood. We recorded from the substantia nigra pars reticulata (SNR), the major basal ganglia output nucleus, during self-initiated drinking in mice. The firing rates of many lateral SNR neurons were time-locked to individual licks. These neurons send GABAergic projections to the deep layers of the orofacial region of the lateral tectum (superior colliculus, SC). Many tectal neurons were also time-locked to licking, but their activity was usually in antiphase with that of SNR neurons, suggesting inhibitory nigrotectal projections. We used optogenetics to selectively activate the GABAergic nigrotectal afferents in the deep layers of the SC. Photo-stimulation of the nigrotectal projections transiently inhibited the activity of the lick-related tectal neurons, disrupted their licking-related oscillatory pattern and suppressed self-initiated drinking. These results demonstrate that GABAergic nigrotectal projections have a crucial role in coordinating drinking behavior.
Authors
Rossi, MA; Li, HE; Lu, D; Kim, IH; Bartholomew, RA; Gaidis, E; Barter, JW; Kim, N; Cai, MT; Soderling, SH; Yin, HH
MLA Citation
Rossi, Mark A., et al. “A GABAergic nigrotectal pathway for coordination of drinking behavior..” Nat Neurosci, vol. 19, no. 5, May 2016, pp. 742–48. Pubmed, doi:10.1038/nn.4285.
URI
https://scholars.duke.edu/individual/pub1127751
PMID
27043290
Source
pubmed
Published In
Nat Neurosci
Volume
19
Published Date
Start Page
742
End Page
748
DOI
10.1038/nn.4285

Research Areas:

3',5'-Cyclic-AMP Phosphodiesterases
3',5'-Cyclic-GMP Phosphodiesterases
Actin Cytoskeleton
Actin-Related Protein 2-3 Complex
Actins
Alternative Splicing
Amino Acid Sequence
Animals
Animals, Newborn
Avoidance Learning
Bacterial Proteins
Base Sequence
Binding Sites
Blotting, Northern
Blotting, Southern
Brain
Brain Chemistry
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Catalysis
Cell Compartmentation
Cell Line
Cell Membrane
Cell Movement
Cell Polarity
Cells, Cultured
Cercopithecus aethiops
Cerebral Ventricles
Chromosomes, Artificial, Bacterial
Cloning, Molecular
Computational Biology
Consensus Sequence
Cyclic AMP
Cyclic AMP-Dependent Protein Kinase Type II
Cyclic AMP-Dependent Protein Kinases
Cyclic GMP
Cyclic Nucleotide Phosphodiesterases, Type 1
Cyclic Nucleotide Phosphodiesterases, Type 7
Cytoskeletal Proteins
Cytoskeleton
DNA, Complementary
Databases as Topic
Dendritic Spines
Dimerization
Disease Models, Animal
Endocytosis
Enzyme Inhibitors
Epidermis
Exploratory Behavior
Expressed Sequence Tags
Fertility
Fluorescent Dyes
GTPase-Activating Proteins
Gene Deletion
Gene Expression
Gene Expression Regulation
Gene Expression Regulation, Developmental
Genetic Variation
Green Fluorescent Proteins
HEK293 Cells
HeLa Cells
Hippocampus
Homeostasis
Humans
Hydrocephalus
Immunohistochemistry
In Situ Hybridization, Fluorescence
Indoles
Insulin
Intracellular Signaling Peptides and Proteins
Isoenzymes
Keratinocytes
Kinetics
Learning
Lipid Metabolism
Liposomes
Luminescent Proteins
Lymphocyte Activation
Macrophages
Magnetic Resonance Imaging
Male
Mass Spectrometry
Matrix Attachment Regions
Maze Learning
Memory
Memory Disorders
Mental Disorders
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microarray Analysis
Microfilament Proteins
Microscopy, Electron
Microscopy, Electron, Scanning
Models, Biological
Models, Chemical
Models, Molecular
Molecular Sequence Data
Molecular Weight
Motor Activity
Multiprotein Complexes
Nerve Tissue Proteins
Neuronal Plasticity
Neurons
Neuropsychological Tests
Open Reading Frames
Organic Chemicals
Penile Erection
Peptide Fragments
Peptide Library
Peptide Mapping
Phosphatidylinositols
Phosphoproteins
Phosphoric Diester Hydrolases
Phosphorylation
Phosphotransferases (Alcohol Group Acceptor)
Photobleaching
Potassium Channels
Presynaptic Terminals
Protein Binding
Protein Conformation
Protein Engineering
Protein Interaction Domains and Motifs
Protein Isoforms
Protein Structure, Tertiary
Proteins
Proteomics
RNA, Messenger
RNA, Untranslated
Rats
Rats, Sprague-Dawley
Receptors, GABA-A
Receptors, Glutamate
Recombinant Proteins
Reflex, Startle
Restriction Mapping
Sensation
Sequence Alignment
Sequence Homology, Amino Acid
Signal Transduction
Social Behavior
Sperm Motility
Sperm Tail
Spermatozoa
Startle Reaction
Stem Cells
Subcellular Fractions
Substrate Specificity
Synapses
Synaptic Transmission
T-Lymphocytes
Testis
Thiophenes
Time Factors
Wiskott-Aldrich Syndrome
Wiskott-Aldrich Syndrome Protein Family
rac GTP-Binding Proteins
rac1 GTP-Binding Protein
src Homology Domains