The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines
Open accessAbstract
NMDA-type glutamate receptors play a critical role in the activity-dependent development and structural remodeling of dendritic arbors and spines. However, the molecular mechanisms that link NMDA receptor activation to changes in dendritic morphology remain unclear. We report that the Rac1-GEF Tiam1 is present in dendrites and spines and is required for their development. Tiam1 interacts with the NMDA receptor and is phosphorylated in a calcium-dependent manner in response to NMDA receptor stimulation. Blockade of Tiam1 function with RNAi and dominant interfering mutants of Tiam1 suggests that Tiam1 mediates effects of the NMDA receptor on dendritic development by inducing Rac1-dependent actin remodeling and protein synthesis. Taken together, these findings define a molecular mechanism by which NMDA receptor signaling controls the growth and morphology of dendritic arbors and spines.
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Tiam1 is the major Rac guanine nucleotide exchange factor that couples NMDAR to Rac1.
“It has previously been reported that c-jun-terminal kinase interacting proteins 1/2 (JIP1/2) interact with ApoER2 (Stockinger et al., 2000) as well as Tiam1 (Buchsbaum et al., 2002), the major Rac guanine nucleotide exchange factor that couples the NMDAR to Rac1 (Tolias et al., 2005).”
From The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning (2017) · cites this paper as Tolias et al., 2005
The Introduction (p. 1) identifies Tiam1 as a Rac1-specific GEF, and the Discussion (p. 10) says it activates Rac1 in response to NMDA receptor stimulation. The paper does not establish that Tiam1 is the *major* GEF coupling the receptor to Rac1; it also says the precise coupling mechanism remains to be determined (Discussion, p. 9). (LLM, conf=0.86)
Experimental — accuracy not yet measuredTiam1 is a Rac-GEF implicated in activity-dependent remodeling of dendritic arbors and is responsible for coupling between NMDAR and Rac1.
“One Rac-GEF implicated in the activity-dependent remodeling of dendritic arbors is Tiam1, which is responsible for the coupling between NMDAR and Rac1 (Tolias et al., 2005).”
From The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning (2017) · cites this paper as Tolias et al., 2005
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- Authors
- Tolias, K. F., Bikoff, J. B., Burette, A., Paradis, S., Harrar, D., Tavazoie, S., Weinberg, R. J., & Greenberg, M. E.
- Affiliations
- Boston Children's Hospital (US)
- University of North Carolina at Chapel Hill (US)
- Harvard University (US)
- Corresponding author
- Greenberg, Michael E.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 45
- Issue
- 4
- Pages
- 525-538
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1977679299
- Cited by
- 365
- References
- 6
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 8 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 13 · 2017: 14 · 2016: 18 · 2015: 19 · 2014: 20 · 2013: 30 · 2012: 20
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (5r01ns045500-29)
- National Institute of Neurological Disorders and Stroke (R01-NS-045500, R01NS039444, NS-07484, NS-39444, NS 44306, NS-04550, P01NS044306)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Tiam1, Rac1, NMDA receptor, dendritic spines, dendritic arbor development, actin cytoskeleton remodeling, calcium-dependent phosphorylation, protein synthesis, glutamate receptor signaling, dendritic morphology
- MeSH terms
- T-Lymphoma Invasion and Metastasis-inducing Protein 1, Animals, Animals, Newborn, Brain, Calcium, Cell Line, Cloning, Molecular, DNA-Binding Proteins, Drug Interactions, Egtazic Acid, Humans, Immunohistochemistry, Models, Neurological, Neoplasm Proteins, Neurons, Proteins, Synaptosomes, Tetrodotoxin, Time Factors, Transcription Factors, Transfection, Valine, Blotting, Western, Receptors, N-Methyl-D-Aspartate, Microscopy, Immunoelectron, RNA, Antisense, Protein Serine-Threonine Kinases, Gene Expression Regulation, Developmental, Excitatory Amino Acid Antagonists, Glutamic Acid, 6-Cyano-7-nitroquinoxaline-2,3-dione, Guanine Nucleotide Exchange Factors, rac1 GTP-Binding Protein, RNA, Small Interfering, Ephrin-B1, Immunoprecipitation, Cell Size, Dendritic Spines, Green Fluorescent Proteins, Rats, p21-Activated Kinases
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