ADP-ribosylation factor-like 4C binding to filamin-A modulates filopodium formation and cell migration

被引:27
作者
Chiang, Tsai-Shin [1 ]
Wu, Hsu-Feng [1 ]
Lee, Fang-Jen S. [1 ,2 ]
机构
[1] Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei 100, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Med Res, Taipei 100, Taiwan
关键词
ARF FAMILY; NUCLEOTIDE-EXCHANGE; SAR PROTEINS; CDC42; GTPASES; LOCALIZATION; TRANSPORT; POLARITY; COMPLEX; GROWTH;
D O I
10.1091/mbc.E17-01-0059
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Changes in cell morphology and the physical forces that occur during migration are generated by a dynamic filamentous actin cytoskeleton. The ADP-ribosylation factor-like 4C (Arl4C) small GTPase acts as a molecular switch to regulate morphological changes and cell migration, although the mechanism by which this occurs remains unclear. Here we report that Arl4C functions with the actin regulator filamin-A (FLNa) to modulate filopodium formation and cell migration. We found that Arl4C interacted with FLNa in a GTP-dependent manner and that FLNa IgG repeat 22 is both required and sufficient for this interaction. We also show that interaction between FLNa and Arl4C is essential for Arl4C-induced filopodium formation and increases the association of FLNa with Cdc42-GEF FGD6, promoting cell division cycle 42 (Cdc42) GTPase activation. Thus our study revealed a novel mechanism, whereby filopodium formation and cell migration are regulated through the Arl4C-FLNa-mediated activation of Cdc42.
引用
收藏
页码:3013 / 3028
页数:16
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