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Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone

Abstract

Precisely regulated radial migration out of the ventricular zone is essential for corticogenesis. Here, we identify a mechanism that can tether ventricular zone cells in situ. FILIP interacts with Filamin A, an indispensable actin-binding protein that is required for cell motility, and induces its degradation in COS-7 cells. Degradation of Filamin A is identified in the cortical ventricular zone, where filip mRNA is localized. Furthermore, most ventricular zone cells that overexpress FILIP fail to migrate in explants. These results demonstrate that FILIP functions through a Filamin A–F-actin axis to control the start of neocortical cell migration from the ventricular zone.

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Figure 1: Expression and structure of FILIPs.
Figure 2: FILIPs are cytoskeleton-associated proteins.
Figure 3: FILIPs interact with an actin-binding protein, Filamin A.
Figure 4: FILIPs suppress cell motility and the formation of lamellipodia in COS-7 cells.
Figure 5: FILIPs induce degradation of Filamin A.
Figure 6: FILIPs suppress radial cell migration in neocortical explants.
Figure 7: L-FILIP interacts dominantly with Filamin A in the developing neocortex.

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Acknowledgements

We thank S. Morikubo, S. Funai, H. Yoshikawa, T. Kato, D. Konno, Y. Takamura and M. Maeda for their technical assistance, H. Yagi, K. Ando, T. Nakamura, T. Takami for helpful discussions, Y. Yokota for critical reading and H. Takagi for encouragement. We are also grateful to T. Stossel and Y. Ohta for the human Filamin A cDNA and J. Miyazaki for the pCAGGS vector. Image analysis by confocal microscopy (LSM510) was supported by the Center for Analytical Instruments, National Institute for Basic Biology. This work was supported in part by the Ministry of Education, Culture, Sports, Science and Technology (to M.S. and T.N.), the Kato Memorial Bioscience Foundation (to M.S.) and the Japan Spina Bifida & Hydrocephalus Research Foundation (to M.S.).

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Correspondence to Makoto Sato.

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Nagano, T., Yoneda, T., Hatanaka, Y. et al. Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone. Nat Cell Biol 4, 495–501 (2002). https://doi.org/10.1038/ncb808

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