Loss of βPix Causes Defects in Early Embryonic Development, and Cell Spreading and PlateletDerived Growth Factor-Induced Chemotaxis in Mouse Embryonic Fibroblasts
TaeIn Kang1,3, Seung Joon Lee2,3, Younghee Kwon1,3, and Dongeun Park1,*
1School of Biological Sciences, Seoul National University, Seoul 08826, Korea, 2Computational Biology & Genomics, Biogen,Cambridge, MA 02142, USA, 3These authors contributed equally to this work.
Received June 24, 2019; Revised July 11, 2019; Accepted July 12, 2019.; Published online August 9, 2019.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

ABSTRACT
βPix is a guanine nucleotide exchange factor for the Rho family small GTPases, Rac1 and Cdc42. It is known to regulate focal adhesion dynamics and cell migration. However, the in vivo role of βPix is currently not well understood. Here, we report the production and characterization of βPix-KO mice. Loss of βPix results in embryonic lethality accompanied by abnormal developmental features, such as incomplete neural tube closure, impaired axial rotation, and failure of allantoischorion fusion. We also generated βPix-KO mouse embryonic fibroblasts (MEFs) to examine βPix function in mouse fibroblasts. βPix-KO MEFs exhibit decreased Rac1 activity, and defects in cell spreading and platelet-derived growth factor (PDGF)-induced ruffle formation and chemotaxis. The average size of focal adhesions is increased in βPix-KO MEFs. Interestingly, βPix-KO MEFs showed increased motility in random migration and rapid wound healing with elevated levels of MLC2 phosphorylation. Taken together, our data demonstrate that βPix plays essential roles in early embryonic development, cell spreading, and cell migration in fibroblasts.
Keywords: βPix, cell motility, embryonic lethality, focal adhesion, mouse embryonic fibroblast


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31 July 2019 Volume 42,
Number 7, pp. 503~567

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