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

被引:28
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
相关论文
共 54 条
[41]  
Ridley Anne J., 1999, P111
[42]  
SCHURMANN A, 1994, J BIOL CHEM, V269, P15683
[43]   Crystal structure of the dimerization domain of human filamin A [J].
Seo, Min-Duk ;
Seok, Seung-Hyeon ;
Im, Hookang ;
Kwon, Ae-Ran ;
Lee, Sang Jae ;
Kim, Hyung-Ryong ;
Cho, Yongicheol ;
Park, Dongeun ;
Lee, Bong-Jin .
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2009, 75 (01) :258-263
[44]   The Cdc42 Guanine Nucleotide Exchange Factor FGD6 Coordinates Cell Polarity and Endosomal Membrane Recycling in Osteoclasts [J].
Steenblock, Charlotte ;
Heckel, Tobias ;
Czupalla, Cornelia ;
Santo, Ana Isabel Espirito ;
Niehage, Christian ;
Sztacho, Martin ;
Hoflack, Bernard .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (26) :18347-18359
[45]   Filamins as integrators of cell mechanics and signalling [J].
Stossel, TP ;
Condeelis, J ;
Cooley, L ;
Hartwig, JH ;
Noegel, A ;
Schleicher, M ;
Shapiro, SS .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2001, 2 (02) :138-145
[46]  
Su D, 2015, AM J TRANSL RES, V7, P242
[47]   The Neural Cell Adhesion Molecule (NCAM) Promotes Clustering and Activation of EphA3 Receptors in GABAergic Interneurons to Induce Ras Homolog Gene Family, Member A (RhoA)/Rho-associated protein kinase (ROCK)-mediated Growth Cone Collapse [J].
Sullivan, Chelsea S. ;
Kumper, Maike ;
Temple, Brenda S. ;
Maness, Patricia F. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291 (51) :26262-26272
[48]   An antiproliferative gene FLNA regulates migration and invasion of gastric carcinoma cell in vitro and its clinical significance [J].
Sun, G. G. ;
Sheng, S. H. ;
Jing, S. W. ;
Hu, W. N. .
TUMOR BIOLOGY, 2014, 35 (03) :2641-2648
[49]   Small GTP-binding proteins [J].
Takai, Y ;
Sasaki, T ;
Matozaki, T .
PHYSIOLOGICAL REVIEWS, 2001, 81 (01) :153-208
[50]   Structural and functional aspects of filamins [J].
van der Flier, A ;
Sonnenberg, A .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2001, 1538 (2-3) :99-117