共 54 条
ADP-ribosylation factor-like 4C binding to filamin-A modulates filopodium formation and cell migration
被引:28
作者:

Chiang, Tsai-Shin
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机构:
Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei 100, Taiwan Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei 100, Taiwan

Wu, Hsu-Feng
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h-index: 0
机构:
Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei 100, Taiwan Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei 100, Taiwan

Lee, Fang-Jen S.
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机构:
Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei 100, Taiwan
Natl Taiwan Univ Hosp, Dept Med Res, Taipei 100, Taiwan Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei 100, Taiwan
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.
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页码:3013 / 3028
页数:16
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