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Arl4A‐PAK1 complex establishes a positive‐feedback loop contributing to PAK1 activation for cell migration
Author(s) -
Lee FangJen Scott,
Chen KuanJung,
Chiang TsaiChen,
Yu ChiaJung
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb276
Subject(s) - pak1 , microbiology and biotechnology , gtpase , cytoskeleton , actin cytoskeleton , guanine nucleotide exchange factor , cell migration , cdc42 , biology , actin , cytoplasm , actin remodeling , rac1 , cell membrane , cell cortex , gtp binding protein regulators , signal transduction , cell , g protein , biochemistry
Cell migration requires coordination of multiple signaling pathways involving in membrane dynamic and cytoskeleton rearrangement. Arf‐like small GTPase Arl4A has been shown to modulate the Golgi organization and actin cytoskeleton remodeling. However, the evidences for Arl4A function in cell migration are insufficient. Here, we report that Arl4A acts with a serine/threonine protein kinase PAK1 to modulate cell migration. We first observe that Arl4A directly interacts with PAK1, and recruits PAK1 to the plasma membrane in a GTP‐dependent manner. Unexpectedly, we found that PAK1 can recruit a cytoplasmic myristoylation‐deficient Arl4A‐G2A mutant, but not GTP‐binding defective Arl4A‐T34N mutant, to the plasma membrane. Thus, these results suggest that there is a positive feedback loop between Arl4A and PAK1, which mutually recruit each other to the plasma membrane. Furthermore, we found that Arl4A promotes cell migration in a GTP‐dependent manner and Arl4A‐PAK1 interaction is critical for Arl4A‐induced cell migration, which is independent of Rac‐PAK1 interaction. Overall, this study shows that Arl4A plays important role for cell migration through direct interaction of PAK1 without effecting Rac1 activation. Our data presented here provide evidence for a novel mechanism for PAK1 regulation and activation. Support or Funding Information This work was supported by grants from the NHRI in Taiwan (NHRI‐EX106‐10601B1) to F.‐J. S. Lee This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .