ArticleProceedings of the National Academy of Sciences of the United States of America2020
CRL5-dependent regulation of the small GTPases ARL4C and ARF6 controls hippocampal morphogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 14 citations in OpenAlex.
- Implications of ADP-Ribosylation Factor-Like Protein 4C (ARL4C) in Human Neoplasia With Special Emphasis on Ameloblastoma: A Scoping Review.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- Uncoupling neocortical neuron fate and migration via a Let-7-RBX2 axis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Targeting the ARL4C/RAP1/PI3K-Akt-mTOR signaling loop promotes ARL4C ubiquitination and reverses oxaliplatin resistance in colorectal cancer.Theranostics · 2026Article
- Structural variant landscape provides insights into genome organisation and domestication in European seabass.BMC biology · 2025Article
- The potential of ARL4C and its-mediated genes in atherosclerosis and agent development.Frontiers in pharmacology · 2025Review
- Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression.Oncology reports · 2024Article
- Identification of biomarkers and potential drug targets in osteoarthritis based on bioinformatics analysis and mendelian randomization.Frontiers in pharmacology · 2024Article
- Notch directs telencephalic development and controls neocortical neuron fate determination by regulating microRNA levels.Development (Cambridge, England) · 2023Article
- Ubiquitin and its relatives as wizards of the endolysosomal system.Journal of cell science · 2023Article
- Tumor Microenvironment and Genes Affecting the Prognosis of Temozolomide-Treated Glioblastoma.Journal of personalized medicine · 2023Article
- Phosphorylation of Arl4A/D promotes their binding by the HYPK chaperone for their stable recruitment to the plasma membrane.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Physiological and Pathological Roles of the Cytohesin Family in Neurons.International journal of molecular sciences · 2022Review
- The E3 Ubiquitin Ligase CRL5 Regulates Dentate Gyrus Morphogenesis, Adult Neurogenesis, and Animal Behavior.Frontiers in neuroscience · 2022Article
- Ubiquitination-Dependent Regulation of Small GTPases in Membrane Trafficking: From Cell Biology to Human Diseases.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The small GTPase ARL4C participates in the regulation of cell migration, cytoskeletal rearrangements, and vesicular trafficking in epithelial cells. The ARL4C signaling cascade starts by the recruitment of the ARF-GEF cytohesins to the plasma membrane, which, in turn, bind and activate the small GTPase ARF6. However, the role of ARL4C-cytohesin-ARF6 signaling during hippocampal development remains elusive. Here, we report that the E3 ubiquitin ligase Cullin 5/RBX2 (CRL5) controls the stability of ARL4C and its signaling effectors to regulate hippocampal morphogenesis. Both RBX2 knockout and Cullin 5 knockdown cause hippocampal pyramidal neuron mislocalization and development of multiple apical dendrites. We used quantitative mass spectrometry to show that ARL4C, Cytohesin-1/3, and ARF6 accumulate in the RBX2 mutant telencephalon. Furthermore, we show that depletion of ARL4C rescues the phenotypes caused by Cullin 5 knockdown, whereas depletion of CYTH1 or ARF6 exacerbates overmigration. Finally, we show that ARL4C, CYTH1, and ARF6 are necessary for the dendritic outgrowth of pyramidal neurons to the superficial strata of the hippocampus. Overall, we identified CRL5 as a key regulator of hippocampal development and uncovered ARL4C, CYTH1, and ARF6 as CRL5-regulated signaling effectors that control pyramidal neuron migration and dendritogenesis.
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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.