ArticleJournal of cell science2013
PDGFRα signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 95 citations in OpenAlex.
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- Primary cilia and neural computation.Journal of biomedical science · 2026Review
- Proximity labeling proteomics maps radial glial ciliary proteins across the developing telencephalon.Cell reports · 2026Article
- CAR-T cell immunotherapy in rhabdomyosarcoma.Journal of translational medicine · 2026Review
- The primary cilium as a multifunctional organelle: emerging roles and unanswered questions.Cell communication and signaling : CCS · 2025Review
- FGFR2 residence in primary cilia is necessary for epithelial cell signaling.The Journal of cell biology · 2025Article
- A role for pH dynamics regulating transcription factor DNA-binding selectivity.Nucleic acids research · 2025Article
- Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling.Hepatology (Baltimore, Md.) · 2025Article
- Neuronal guidance behaviours: the primary cilium perspective.Frontiers in cell and developmental biology · 2025Review
- Increased ER stress by depletion of PDIA6 impairs primary ciliogenesis and enhances sensitivity to ferroptosis in kidney cells.BMB reports · 2024Article
- The electroneutral NaAmerican journal of physiology. Cell physiology · 2024Article
- The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium.Communications biology · 2024Article
- CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration.Nature communications · 2023Article
- Role of Akt/Protein Kinase B in Cancer Metastasis.Biomedicines · 2023Review
- Enhanced primary ciliogenesis via mitochondrial oxidative stress activates AKT to prevent neurotoxicity in HSPA9/mortalin-depleted SH-SY5Y cells.Molecular brain · 2023Article
- Ciliopathies in pediatric endocrinology.Annals of pediatric endocrinology & metabolism · 2023Article
- The Primary Cilium and Neuronal Migration.Cells · 2022Review
- Hippocampals neurogenesis is impaired in mice with a deletion in the coiled coil domain of Talpid3-implications for Joubert syndrome.Human molecular genetics · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- Crosstalk between Sodium-Glucose Cotransporter Inhibitors and Sodium-Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases.International journal of molecular sciences · 2021Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
In fibroblasts, platelet-derived growth factor receptor alpha (PDGFRα) is upregulated during growth arrest and compartmentalized to the primary cilium. PDGF-AA mediated activation of the dimerized ciliary receptor produces a phosphorylation cascade through the PI3K-AKT and MEK1/2-ERK1/2 pathways leading to the activation of the Na(+)/H(+) exchanger, NHE1, cytoplasmic alkalinization and actin nucleation at the lamellipodium that supports directional cell migration. We here show that AKT and MEK1/2-ERK1/2-p90(RSK) inhibition reduced PDGF-AA-induced cell migration by distinct mechanisms: AKT inhibition reduced NHE1 activity by blocking the translocation of NHE1 to the cell membrane. MEK1/2 inhibition did not affect NHE1 activity but influenced NHE1 localization, causing NHE1 to localize discontinuously in patches along the plasma membrane, rather than preferentially at the lamellipodium. We also provide direct evidence of NHE1 translocation through the cytoplasm to the leading edge. In conclusion, signals initiated at the primary cilium through the PDGFRαα cascade reorganize the cytoskeleton to regulate cell migration differentially through the AKT and the MEK1/2-ERK1/2-p90(RSK) pathways. The AKT pathway is necessary for initiation of NHE1 translocation, presumably in vesicles, to the leading edge and for its activation. In contrast, the MEK1/2-ERK1/2-p90(RSK) pathway controls the spatial organization of NHE1 translocation and incorporation, and therefore specifies the direction of the leading edge formation.
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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.