ArticleMolecular biology of the cell2014
Rab35, acting through ACAP2 switching off Arf6, negatively regulates oligodendrocyte differentiation and myelination.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Gene expression profiles of endothelium, microglia and oligodendrocytes in hippocampus of post-stroke depression rat at single cell resolution.Molecular psychiatry · 2025Article
- Arf6 is required for endocytosis and filamentous actin assembly during angiogenesis in vitro.Microcirculation (New York, N.Y. : 1994) · 2023Article
- Role of SNAREs and Rabs in Myelin Regulation.International journal of molecular sciences · 2023Review
- RAB35 is required for murine hippocampal development and functions by regulating neuronal cell distribution.Communications biology · 2023Article
- Arf6 Regulates Endocytosis and Angiogenesis by Promoting Filamentous Actin Assembly.bioRxiv : the preprint server for biology · 2023Article
- Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases.bioRxiv : the preprint server for biology · 2023Article
- Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis.Nature communications · 2022Article
- Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- TBC1D10C is a cytoskeletal functional linker that modulates cell spreading and phagocytosis in macrophages.Scientific reports · 2021Article
- Rab22a regulates the establishment of epithelial polarity.Small GTPases · 2021Article
- Rnd2 differentially regulates oligodendrocyte myelination at different developmental periods.Molecular biology of the cell · 2021Article
- An Arf/Rab cascade controls the growth and invasiveness of glioblastoma.The Journal of cell biology · 2021Article
- CREB3L2 Modulates Nerve Growth Factor-Induced Cell Differentiation.Frontiers in molecular neuroscience · 2021Article
- The role of the oncogenic Rab35 in cancer invasion, metastasis, and immune evasion, especially in leukemia.Small GTPases · 2020Review
- Rab35-regulated lipid turnover by myotubularins represses mTORC1 activity and controls myelin growth.Nature communications · 2020Article
- The Recycling Endosome in Nerve Cell Development: One Rab to Rule Them All?Frontiers in cell and developmental biology · 2020Review
- Coordinated Regulation of Intracellular Fascin Distribution Governs Tumor Microvesicle Release and Invasive Cell Capacity.Molecular and cellular biology · 2019Article
- Coordination of synaptic vesicle trafficking and turnover by the Rab35 signaling network.Small GTPases · 2019Review
- RAB-35 and ARF-6 GTPases Mediate Engulfment and Clearance Following Linker Cell-Type Death.Developmental cell · 2018Article
- Aberrant endocytosis leads to the loss of normal mitotic spindle orientation during epithelial glandular morphogenesis.The Journal of biological chemistry · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oligodendrocyte precursor cells differentiate to produce myelin sheaths that insulate axons to ensure fast propagation of action potentials. Many aspects of differentiation are regulated by multiple extracellular signals. However, their intracellular signalings remain elusive. We show that Rab35 and its effector, ACAP2, a GTPase-activating protein that switches off Arf6 activity, negatively regulate oligodendrocyte morphological differentiation. Knockdown of Rab35 or ACAP2 with their respective small interfering RNAs promotes differentiation. As differentiation initiates, the activities of Rab35 and ACAP2 are down-regulated. The activity of Arf6, in contrast, is up-regulated. Arf6 knockdown inhibits differentiation, indicating that Rab35 and ACAP2 negatively regulate differentiation by down-regulating Arf6. Importantly, as differentiation proceeds, the activity of cytohesin-2, a guanine nucleotide exchange factor that switches on Arf6 activity, is up-regulated. Pharmacological inhibition of cytohesin-2 inhibits differentiation, suggesting that cytohesin-2 promotes differentiation by activating Arf6. Furthermore, using oligodendrocyte-neuronal cocultures, we find that knockdown of Rab35 or ACAP2 promotes myelination, whereas inhibition of cytohesin-2 or knockdown of Arf6 inhibits myelination. Thus Rab35/ACAP2 and cytohesin-2 antagonistically control oligodendrocyte differentiation and myelination through Arf6 regulation, presenting a unique small GTPase on/off switching mechanism.
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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.