ArticleProceedings of the National Academy of Sciences of the United States of America2006
TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 141 citations in OpenAlex.
- Irisin-BDNF axis mediates muscle-brain communication: a complete molecular cascade and potential bidirectional feedback from peripheral activation to central protection.Biogerontology · 2026Review
- TIAM1 drives prostatic branching phenotype and is a potential therapeutic target for benign prostatic hyperplasia.JCI insight · 2025Article
- Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia.Brain : a journal of neurology · 2024Article
- Tiam1 coordinates synaptic structural and functional plasticity underpinning the pathophysiology of neuropathic pain.Neuron · 2023Article
- c-Abl Tyrosine Kinase Is Required for BDNF-Induced Dendritic Branching and Growth.International journal of molecular sciences · 2023Article
- Extracellular molecular signals shaping dendrite architecture during brain development.Frontiers in cell and developmental biology · 2023Review
- FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway.Journal of cellular and molecular medicine · 2022Article
- Proteomic alteration of endometrial tissues during secretion in polycystic ovary syndrome may affect endometrial receptivity.Clinical proteomics · 2022Article
- Loss-of-function variants in TIAM1 are associated with developmental delay, intellectual disability, and seizures.American journal of human genetics · 2022Article
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
- GPCRs thatSmall GTPases · 2022Review
- Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Effects of 7,8-Dihydroxyflavone on Lipid Isoprenoid and Rho Protein Levels in Brains of Aged C57BL/6 Mice.Neuromolecular medicine · 2021Article
- Multiplexed GTPase and GEF biosensor imaging enables network connectivity analysis.Nature chemical biology · 2020Article
- Myelin-associated glycoprotein inhibits neurite outgrowth through inactivation of the small GTPase Rap1.FEBS letters · 2020Article
- TrkB hyperactivity contributes to brain dysconnectivity, epileptogenesis, and anxiety in zebrafish model of Tuberous Sclerosis Complex.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling.Cell reports · 2019Article
- Review
- Prefrontal cortical trkB, glucocorticoids, and their interactions in stress and developmental contexts.Neuroscience and biobehavioral reviews · 2018Review
- The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear Extinction Circuitry and Behavior.Neuron · 2018Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Small GTPases of the Rho family play key roles in the formation of neuronal axons and dendrites by transducing signals from guidance cues, such as neurotrophins, to the actin cytoskeleton. However, there is little insight into the mechanism by which neurotrophins regulate Rho GTPases. Here, we show the crucial role of the ubiquitous Rac1-specific guanine nucleotide exchange factor, Tiam1 (T lymphoma invasion and metastasis 1), in transducing a neurotrophin-mediated change in cell shape. We demonstrate that BDNF, acting through TrkB, directly binds and specifically activates Tiam1 by phosphorylating Tyr-829, leading to Rac1 activation and lamellipodia formation in Cos-7 cells and increased neurite outgrowth from cortical neurons. A point mutation in Tiam1, Tyr-829 to Phe-829, blocked these BDNF-induced changes in cellular morphology. The findings are evidence of a previously uncharacterized mechanism for the activation of Tiam1 and of a role for this effector in neurotrophin-mediated signal transduction leading to changes in cellular morphology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.