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

• Published in: Molecular biology of the cell Vol. 28; no. 22; pp. 3013 - 3028
• Main Authors: Chiang, Tsai-Shin, Wu, Hsu-Feng, Lee, Fang-Jen S.
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 01.11.2017
• Subjects: Actin Cytoskeleton - metabolism; Actins; ADP-Ribosylation; ADP-Ribosylation Factors - metabolism; ADP-Ribosylation Factors - physiology; Animals; cdc42 GTP-Binding Protein - metabolism; Cell Movement - physiology; Filamins - metabolism; Filamins - physiology; HeLa Cells; Humans; Microfilament Proteins - metabolism; Neoplasm Metastasis - physiopathology; Neoplasms - metabolism; Pseudopodia - metabolism
• ISSN: 1059-1524; 1939-4586; 1939-4586
• DOI: 10.1091/mbc.e17-01-0059

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.