Type I collagen-induced YAP nuclear expression promotes primary cilia growth and contributes to cell migration in confluent mouse embryo fibroblast 3T3-L1 cells
The extracellular matrix (ECM) is a major biomechanical environment for all cells in vivo, and tightly controls wound healing and cancer progression. Type I collagen (Col I) is the most abundant component in ECM and plays an essential role for cell motility control and migration beyond structural support. Our previous results showed that Col I increased the length of primary cilia and the expression of primary cilia-associated proteins in 3T3-L1 cells. The Hippo/YAP pathway serves as a major integrator of cell surface-mediated signals and regulates key processes for the development and maintenance of tissue functions. In this study, we investigated the role of Hippo/YAP signaling in primary cilia growth of cells cultured on Col I-coated plate, as well as the potential link between primary cilia and migration. At 2-day post-confluence, YAP localization in the nucleus was dramatically increased when the cells were cultured on Col I-coated plate, accompanied by cilia growth. YAP inhibitor verteporfin repressed the growth of primary cilia as well as the expressions of ciliogenesis-associated proteins in confluent 3T3-L1 cells cultured on Col I-coated plate. Moreover, knockdown of either YAP or IFT88, one of the ciliogenesis-associated proteins, reversed the migration of confluent 3T3-L1 cells promoted by Col I-coating. In conclusion, activation of YAP pathway by Col I-coating of culture plate for confluent 3T3-L1 cells is positively associated with the primary cilia growth, which eventually results in promoted migration.
KeywordsCollagen Primary cilia YAP Cell migration 3T3-L1 cells
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Conflict of interest
The authors declare that they have no competing interests.
- 5.Xu Q, Liu W, Liu X, Otkur W, Hayashi T, Yamato M, Fujisaki H, Hattori S, Tashiro SI, Ikejima T (2018) Type I collagen promotes primary cilia growth through down-regulating HDAC6-mediated autophagy in confluent mouse embryo fibroblast 3T3-L1 cells. J Biosci Bioeng 125:8–14. https://doi.org/10.1016/j.jbiosc.2017.07.012 CrossRefGoogle Scholar
- 16.Xu Q, Liu W, Liu X, Otkur W, Hayashi T, Yamato M, Fujisaki H, Hattori S, Tashiro SI, Ikejima T (2017) Type I collagen promotes primary cilia growth through down-regulating HDAC6-mediated autophagy in confluent mouse embryo fibroblast 3T3-L1 cells. J Biosci Bioeng. https://doi.org/10.1016/j.jbiosc.2017.07.012 Google Scholar
- 24.Smith LA, Bukanov NO, Husson H, Russo RJ, Barry TC, Taylor AL, Beier DR, Ibraghimov-Beskrovnaya O (2006) Development of polycystic kidney disease in juvenile cystic kidney mice: insights into pathogenesis, ciliary abnormalities, and common features with human disease. J Am Soc Nephrol 17:2821–2831. https://doi.org/10.1681/ASN.2006020136 CrossRefGoogle Scholar
- 25.den Hollander AI, Koenekoop RK, Yzer S, Lopez I, Arends ML, Voesenek KE, Zonneveld MN, Strom TM, Meitinger T, Brunner HG, Hoyng CB, van den Born LI, Rohrschneider K, Cremers FP (2006) Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. Am J Hum Genet 79:556–561. https://doi.org/10.1086/507318 CrossRefGoogle Scholar
- 26.Christensen ST, Veland IR, Schwab A, Cammer M, Satir P (2013) Analysis of primary cilia in directional cell migration in fibroblasts. Methods Enzymol 525:45–58. https://doi.org/10.1016/B978-0-12-397944-5.00003-1 CrossRefGoogle Scholar
- 27.Schneider L, Cammer M, Lehman J, Nielsen SK, Guerra CF, Veland IR, Stock C, Hoffmann EK, Yoder BK, Schwab A, Satir P, Christensen ST (2010) Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cell Physiol Biochem. https://doi.org/10.1159/000276562 25:279 – 92.Google Scholar
- 30.Muir LA, Neeley CK, Meyer KA, Baker NA, Brosius AM, Washabaugh AR, Varban OA, Finks JF, Zamarron BF, Flesher CG, Chang JS, DelProposto JB, Geletka L, Martinez-Santibanez G, Kaciroti N, Lumeng CN, O’Rourke RW (2016) Adipose tissue fibrosis, hypertrophy, and hyperplasia: correlations with diabetes in human obesity. Obesity (Silver Spring) 24:597–605. https://doi.org/10.1002/oby.21377 CrossRefGoogle Scholar