Poldip2 controls vascular smooth muscle cell migration by regulating focal adhesion turnover and force polarization
Open accessAbstract
Polymerase-δ-interacting protein 2 (Poldip2) interacts with NADPH oxidase 4 (Nox4) and regulates migration; however, the precise underlying mechanisms are unclear. Here, we investigated the role of Poldip2 in focal adhesion turnover, as well as traction force generation and polarization. Poldip2 overexpression (AdPoldip2) in vascular smooth muscle cells (VSMCs) impairs PDGF-induced migration and induces a characteristic phenotype of long cytoplasmic extensions. AdPoldip2 also prevents the decrease in spreading and increased aspect ratio observed in response to PDGF and slightly impairs cell contraction. Moreover, AdPoldip2 blocks focal adhesion dissolution and sustains H 2 O 2 levels in focal adhesions, whereas Poldip2 knockdown (siPoldip2) significantly decreases the number of focal adhesions. RhoA activity is unchanged when focal adhesion dissolution is stimulated in control cells but increases in AdPoldip2-treated cells. Inhibition of RhoA blocks Poldip2-mediated attenuation of focal adhesion dissolution, and overexpression of RhoA or focal adhesion kinase (FAK) reverses the loss of focal adhesions induced by siPoldip2, indicating that RhoA and FAK mediate the effect of Poldip2 on focal adhesions. Nox4 silencing prevents focal adhesion stabilization by AdPoldip2 and induces a phenotype similar to siPoldip2, suggesting a role for Nox4 in Poldip2-induced focal adhesion stability. As a consequence of impaired focal adhesion turnover, PDGF-treated AdPoldip2 cells are unable to reduce and polarize traction forces, a necessary first step in migration. These results implicate Poldip2 in VSMC migration via regulation of focal adhesion turnover and traction force generation in a Nox4/RhoA/FAK-dependent manner.
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The protein polymerase delta-interacting protein 2 (poldip2) seems to exert regulatory effects on NOX4.
“The protein polymerase delta–interacting protein 2 (poldip2) seems to exert regulatory effects on NOX4 (212, 607), although poldip2 is involved on many other pathways (316).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [212]
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References 51 · Cited by 60
Research works printed but not linked: 1
- [28]Mackay DJG, Hall A. Rho GTPases. J Biol Chem 273: 20685–20688, 1998. [DOI] [PubMed] [Google Scholar]
- Authors
- Datla, S. R., McGrail, D. J., Vukelic, S., Huff, L. P., Lyle, A. N., Pounkova, L., Lee, M., Seidel-Rogol, B., Khalil, M. K., Hilenski, L. L., Terada, L. S., Dawson, M. R., Lassègue, B., & Griendling, K. K.
- Affiliations
- Emory University (US)
- Department of Chemical and Biomolecular Engineering and
- Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta;
- The University of Texas Southwestern Medical Center (US)
- Georgia Institute of Technology (US)
- Corresponding author
- Griendling, Kathy K.
- ORCID
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2014-10-01
- Volume
- 307
- Issue
- 7
- Pages
- H945-H957
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC4187069
- OpenAlex
- W2161585597
- Cited by
- 60
- References
- 51
- Citations by year
- 2025: 5 · 2024: 1 · 2023: 7 · 2022: 8 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 6 · 2015: 5
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Georgia Institute of Technology
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL38206, HL058863, R37HL038206, HL-092120, R01HL092120, R01HL058863)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Poldip2, vascular smooth muscle cell migration, focal adhesion turnover, NOX4, RhoA, focal adhesion kinase, PDGF signaling, hydrogen peroxide, cell contraction, cell spreading
- MeSH terms
- NADPH Oxidase 4, Animals, Carrier Proteins, Cell Adhesion, Cell Movement, Hydrogen Peroxide, Muscle, Smooth, Vascular, Platelet-Derived Growth Factor, Cell Polarity, NADPH Oxidases, rhoA GTP-Binding Protein, Focal Adhesions, Myocytes, Smooth Muscle, Rats, Focal Adhesion Protein-Tyrosine Kinases
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