Directional Cell Migration and Chemotaxis in Wound Healing Response to PDGF-AA are Coordinated by the Primary Cilium in Fibroblasts
Open accessAbstract
Cell motility and migration play pivotal roles in numerous physiological and pathophysiological processes including development and tissue repair. Cell migration is regulated through external stimuli such as platelet-derived growth factor-AA (PDGF-AA), a key regulator in directional cell migration during embryonic development and a chemoattractant during postnatal migratory responses including wound healing. We previously showed that PDGFRalpha signaling is coordinated by the primary cilium in quiescent cells. However, little is known about the function of the primary cilium in cell migration. Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88(Tg737Rpw)) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF-AA is absent, leading to unregulated high speed and uncontrolled directional cell displacement during wound closure, with subsequent defects in wound healing. These data suggest that in coordination with cytoskeletal reorganization, the fibroblast primary cilium functions via ciliary PDGFRalpha signaling to monitor directional movement during wound healing.
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In fibroblasts, ciliary PDGFRα signaling activates the PI3K-AKT and MEK1/2-ERK1/2-RSK pathways to control directional cell migration, achieved by targeting NHE1 to the leading edge of migrating cells.
“In fibroblasts, ciliary PDGFRα signalling activates the PI3K–AKT and MEK1/2–ERK1/2–RSK pathways to control directional cell migration, which is achieved by targeting the Na+/H+ exchanger 1, NHE1, to the leading edge of the migrating cells, which project their cilium towards the leading edge and parallel to the path of motility 240, 247–249.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [248]
The Results (‘PDGF-AA signals through Akt at the ciliary base’) show PDGF-AA-dependent PDGFRα and Akt activation, and the Introduction reports that migrating fibroblasts orient their cilia toward the leading edge. The Discussion (‘Conclusions and perspectives’) describes MEK1/2–ERK1/2 signaling and its connection through RSK to NHE1, but treats a link from ciliary signaling to leading-edge NHE1 events as a possibility or hypothesis. It does not establish that ciliary PDGFRα controls migration by targeting NHE1 to the leading edge. No page numbers are provided in our copy. (LLM, conf=0.88)
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References 63 · Cited by 250
- Authors
- Schneider, L., Cammer, M., Lehman, J., Nielsen, S., Guerra, C., Veland, I., Stock, C., Hoffmann, E., Yoder, B., Schwab, A., Satir, P., & Christensen, S.
- Affiliations
- University of Copenhagen (DK)
- Albert Einstein College of Medicine (US)
- University of Alabama at Birmingham (US)
- University of Münster (DE)
- ORCID
- Venue
- Cellular Physiology and Biochemistry
- Publisher
- S. Karger AG
- Published
- 2010
- Volume
- 25
- Issue
- 2-3
- Pages
- 279-292
- ISSN
- 1015-8987 (ISSN-L)
- 1421-9778
- PMC
- PMC2924811
- OpenAlex
- W2081393679
- Cited by
- 250
- References
- 63
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 12 · 2022: 10 · 2021: 17 · 2020: 18 · 2019: 12 · 2018: 23 · 2017: 20 · 2016: 12 · 2015: 22 · 2014: 24 · 2013: 18 · 2012: 25
- FWCI
- 11.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cellular Physiology and Biochemistry (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Kræftens Bekæmpelse
- Stanford Diabetes Research Center
- Deutsche Forschungsgemeinschaft
- Lundbeckfonden
- Westfälische Wilhelms-Universität Münster
- Novo Nordisk Fonden
- H. Lundbeck A/S
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK074038)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052792, P30AR050948)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- primary cilia, directional cell migration, chemotaxis, wound healing, PDGF-AA, PDGFRα signaling, fibroblasts, IFT88, ciliary assembly, cytoskeletal remodeling, chemosensory response
- MeSH terms
- Animals, Cell Movement, Cells, Cultured, Chemotaxis, Cilia, Fibroblasts, Platelet-Derived Growth Factor, Wound Healing, Signal Transduction, Receptor, Platelet-Derived Growth Factor alpha, Tumor Suppressor Proteins, NIH 3T3 Cells, Mice
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