Scott Soderling

Positions:

George Barth Geller Distinguished Professor of Molecular Biology

Cell Biology
School of Medicine

Professor in Cell Biology

Cell Biology
School of Medicine

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:

Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction.

Psychiatric disorders are highly heritable pathologies of altered neural circuit functioning. How genetic mutations lead to specific neural circuit abnormalities underlying behavioral disruptions, however, remains unclear. Using circuit-selective transgenic tools and a mouse model of maladaptive social behavior (ArpC3 mutant), we identify a neural circuit mechanism driving dysfunctional social behavior. We demonstrate that circuit-selective knockout (ctKO) of the ArpC3 gene within prefrontal cortical neurons that project to the basolateral amygdala elevates the excitability of the circuit neurons, leading to disruption of socially evoked neural activity and resulting in abnormal social behavior. Optogenetic activation of this circuit in wild-type mice recapitulates the social dysfunction observed in ArpC3 mutant mice. Finally, the maladaptive sociability of ctKO mice is rescued by optogenetically silencing neurons within this circuit. These results highlight a mechanism of how a gene-to-neural circuit interaction drives altered social behavior, a common phenotype of several psychiatric disorders.
Authors
Kim, IH; Kim, N; Kim, S; Toda, K; Catavero, CM; Courtland, JL; Yin, HH; Soderling, SH
MLA Citation
Kim, Il Hwan, et al. “Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction.Cell Reports, vol. 32, no. 4, July 2020, p. 107965. Epmc, doi:10.1016/j.celrep.2020.107965.
URI
https://scholars.duke.edu/individual/pub1454010
PMID
32726629
Source
epmc
Published In
Cell Reports
Volume
32
Published Date
Start Page
107965
DOI
10.1016/j.celrep.2020.107965

Essential role for InSyn1 in dystroglycan complex integrity and cognitive behaviors in mice.

Human mutations in the dystroglycan complex (DGC) result in not only muscular dystrophy but also cognitive impairments. However, the molecular architecture critical for the synaptic organization of the DGC in neurons remains elusive. Here, we report Inhibitory Synaptic protein 1 (InSyn1) is a critical component of the DGC whose loss alters the composition of the GABAergic synapses, excitatory/inhibitory balance in vitro and in vivo, and cognitive behavior. Association of InSyn1 with DGC subunits is required for InSyn1 synaptic localization. InSyn1 null neurons also show a significant reduction in DGC and GABA receptor distribution as well as abnormal neuronal network activity. Moreover, InSyn1 null mice exhibit elevated neuronal firing patterns in the hippocampus and deficits in fear conditioning memory. Our results support the dysregulation of the DGC at inhibitory synapses and altered neuronal network activity and specific cognitive tasks via loss of a novel component, InSyn1.
Authors
Uezu, A; Hisey, E; Kobayashi, Y; Gao, Y; Bradshaw, TW; Devlin, P; Rodriguiz, R; Tata, PR; Soderling, S
MLA Citation
Uezu, Akiyoshi, et al. “Essential role for InSyn1 in dystroglycan complex integrity and cognitive behaviors in mice.Elife, vol. 8, Dec. 2019. Pubmed, doi:10.7554/eLife.50712.
URI
https://scholars.duke.edu/individual/pub1423146
PMID
31829939
Source
pubmed
Published In
Elife
Volume
8
Published Date
DOI
10.7554/eLife.50712

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

Restored WAVE1 Levels in a Model of NMDA Receptor Hypofunction Attenuates Working Memory Deficits

Authors
Chen, Y; Milenkovic, M; Soderling, SH; Ramsey, AJ
MLA Citation
Chen, Yuxiao, et al. “Restored WAVE1 Levels in a Model of NMDA Receptor Hypofunction Attenuates Working Memory Deficits.” Biological Psychiatry, vol. 77, no. 9, ELSEVIER SCIENCE INC, 2015.
URI
https://scholars.duke.edu/individual/pub1073393
Source
wos
Published In
Biological Psychiatry
Volume
77
Published Date

WASP and WAVE family protein complexes

Arp2/3 is inactive and is unable to trigger de novo actin polymerization. It must be activated by binding to members of the WASP/WAVE family of scaffold proteins to effectively stimulate actin polymerization. The WASP/WAVE family members (WASP, N-WASP, WAVE-1, WAVE-2, and WAVE-3) are activated by Cdc42 and Rac. Thus, a linear pathway (Cdc42/Rac→WASP/WAVE→Arp2/3) translates cellular cues into the assembly of actin filaments. Protein complexes organized by the WASP/WAVE proteins, however, modulate this basic pathway. This chapter summarizes how the WASP and WAVE family protein complexes are organized and are thought to function. WASP/N-WASP and WAVE proteins function as scaffolds to organize protein complexes that modulate dynamic actin turnover through Arp2/3. These protein complexes serve to optimize subcellular targeting of WASP/WAVE, and to act as positive and negative feedback information loops to regulate actin dynamics. Thus, these complexes are likely to serve as sophisticated non-linear signaling pathways that function between Rho-GTPases and Arp2/3. Components of the WASP and WAVE complexes may also function to tie actin regulation to other pathways by interacting with separate protein complexes. Finally, it is likely that new regulatory complexes await discovery. In this regard, WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) has recently been identified as a potential new member of the WASP/WAVE family of Arp2/3 activators. © 2010 Elsevier Inc. All rights reserved.
Authors
Mason, FM; Soderling, SH
MLA Citation
Mason, F. M., and S. H. Soderling. WASP and WAVE family protein complexes. Vol. 2, Dec. 2010, pp. 1265–70. Scopus, doi:10.1016/B978-0-12-374145-5.00157-1.
URI
https://scholars.duke.edu/individual/pub965482
Source
scopus
Volume
2
Published Date
Start Page
1265
End Page
1270
DOI
10.1016/B978-0-12-374145-5.00157-1

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