ArticleThe Journal of biological chemistry2013
The atypical guanine nucleotide exchange factor Dock4 regulates neurite differentiation through modulation of Rac1 GTPase and actin dynamics.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 76 citations in OpenAlex.
- Rho GTPases signaling mediates aggressiveness and differentiation in neuroblastoma tumors.Cell communication and signaling : CCS · 2026Article
- Construction of a novel radioresistance-related signature for prediction of prognosis, immune microenvironment and anti-tumour drug sensitivity in non-small cell lung cancer.Annals of medicine · 2025Article
- Could the Polymorphisms of DOCK4 (rs147636134), SYNGAP1 (rs199759879), and FOXP1 (rs767001715) be the Primary Risk Factors for Bipolar Disorder and Autism Spectrum Disorder?Developmental neurobiology · 2025Article
- Article
- Heterozygous loss-of-function variants in DOCK4 cause neurodevelopmental delay and microcephaly.Human genetics · 2024Article
- Roles of Rac1-Dependent Intrinsic Forgetting in Memory-Related Brain Disorders: Demon or Angel.International journal of molecular sciences · 2023Review
- Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age.Cellular and molecular neurobiology · 2023Article
- Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury.Lipids in health and disease · 2023Article
- Genomic selection analysis of morphological and adaptation traits in Chinese indigenous dog breeds.Frontiers in veterinary science · 2023Article
- eEF2 in the prefrontal cortex promotes excitatory synaptic transmission and social novelty behavior.EMBO reports · 2022Article
- DOCK4 regulates ghrelin production in gastric X/A-like cells.Journal of endocrinological investigation · 2022Article
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
- DOCK4 as a Potential Biomarker Associated with Immune Infiltration in Stomach Adenocarcinoma: A Database Analysis.International journal of general medicine · 2022Article
- Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex.International journal of molecular sciences · 2021Article
- Fusion of single-cell transcriptome and DNA-binding data, for genomic network inference in cortical development.BMC bioinformatics · 2021Article
- The lipid phosphatase-like protein PLPPR1 associates with RhoGDI1 to modulate RhoA activation in response to axon growth inhibitory molecules.Journal of neurochemistry · 2021Article
- Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function.Molecular psychiatry · 2021Article
- Rho GTPases in the Amygdala-A Switch for Fears?Cells · 2020Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Precise regulation of neurite growth and differentiation determines accurate formation of synaptic connections, whose disruptions are frequently associated with neurological disorders. Dedicator of cytokinesis 4 (Dock4), an atypical guanine nucleotide exchange factor for Rac1, is found to be associated with neuropsychiatric diseases, including autism and schizophrenia. Nonetheless, the neuronal function of Dock4 is only beginning to be understood. Using mouse neuroblastoma (Neuro-2a) cells as a model, this study identifies that Dock4 is critical for neurite differentiation and extension. This regulation is through activation of Rac1 and modulation of the dynamics of actin-enriched protrusions on the neurites. In cultured hippocampal neurons, Dock4 regulates the establishment of the axon-dendrite polarity and the arborization of dendrites, two critical processes during neural differentiation. Importantly, a microdeletion Dock4 mutant linked to autism and dyslexia that lacks the GEF domain leads to defective neurite outgrowth and neuronal polarization. Further analysis reveals that the SH3 domain-mediated interaction of Dock4 is required for its activity toward neurite differentiation, whereas its proline-rich C terminus is not essential for this regulation. Together, our findings reveal an important role of Dock4 for neurite differentiation during early neuronal development.
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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.