Abstract:
:Cancer cell migration requires the regulation of actin networks at protrusions associated with invadopodia and other leading edges. Carcinomas become invasive after undergoing an epithelial-mesenchymal transition characterized by the appearance of vimentin filaments. While vimentin expression correlates with cell migration, the molecular connections between vimentin- and actin-based membrane protrusions are not understood. We report here that CARMIL2 (capping protein, Arp2/3, myosin-I linker 2) provides such a molecular link. CARMIL2 localizes to vimentin, regulates actin capping protein (CP), and binds to membranes. CARMIL2 is necessary for invadopodia formation, as well as cell polarity, lamellipodial assembly, membrane ruffling, macropinocytosis, and collective cell migration. Using point mutants and chimeras with defined biochemical and cellular properties, we discovered that localization to vimentin and CP binding are both essential for the function of CARMIL2 in cells. On the basis of these results, we propose a model in which dynamic vimentin filaments target CARMIL2 to critical membrane-associated locations, where CARMIL2 regulates CP, and thus actin assembly, to create cell protrusions.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Lanier MH,Kim T,Cooper JAdoi
10.1091/mbc.E15-08-0552subject
Has Abstractpub_date
2015-12-15 00:00:00pages
4577-88issue
25eissn
1059-1524issn
1939-4586pii
mbc.E15-08-0552journal_volume
26pub_type
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