Formin-like 2 promotes beta 1-integrin trafficking and invasive motility 
downstream of PKC alpha.

Wang, Y.; Arjonen, A.; Pouwels, J.; Ta, H.; Pausch, P.; Bange, G.; Engel, U.; Pan, X. Y.; Fackler, O. T.; Ivaska, J.; Grosse, R.

doi:10.1016/j.devcel.2015.06.015

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Journal Article

Formin-like 2 promotes beta 1-integrin trafficking and invasive motility downstream of PKC alpha.

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Ta, H.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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http://www.sciencedirect.com/science/article/pii/S1534580715004220/pdfft?md5=911c053cf43a49c3912a4c4250d77df2&pid=1-s2.0-S1534580715004220-main.pdf
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2193123_Suppl_1.pdf
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2193123_Suppl_2.mp4
(Supplementary material), 4MB

2193123_Suppl_3.mp4
(Supplementary material), 4MB

2193123_Suppl_4.mp4
(Supplementary material), 16MB

2193123_Suppl_5.mp4
(Supplementary material), 16MB

2193123_Suppl_6.pdf
(Supplementary material), 10MB

Citation

Wang, Y., Arjonen, A., Pouwels, J., Ta, H., Pausch, P., Bange, G., et al. (2015). Formin-like 2 promotes beta 1-integrin trafficking and invasive motility downstream of PKC alpha. Developmental Cell, 34(4), 475-483. doi:10.1016/j.devcel.2015.06.015.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0028-5BB9-4

Abstract

Regulated turnover of integrin receptors is essential for cell adhesion and migration. Pathways selectively regulating beta 1-integrin recycling are implicated in cancer invasion and metastasis, yet proteins required for the internalization of this pro-invasive integrin remain to be identified. Here, we uncover formin-like 2 (FMNL2) as a critical regulator of beta 1-integrin internalization downstream of protein kinase C (PKC). PKC alpha associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition. Phosphorylation of FMNL2 triggers its rapid relocation and promotes its interaction with the cytoplasmic tails of the a-integrin subunits for beta 1-integrin endocytosis. FMNL2 drives beta 1-integrin internalization and invasive motility in a phosphorylationdependent manner, while a FMNL2 mutant defective in actin assembly interferes with beta 1-integrin endocytosis and cancer cell invasion. Our data establish a role for FMNL2 in the regulation of beta 1-integrin and provide a mechanistic understanding of the function of FMNL2 in cancer invasiveness.