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RefilinB (FAM101B) targets filamin A to organize perinuclear actin networks and regulates nuclear shape.


ABSTRACT: The intracellular localization and shape of the nucleus plays a central role in cellular and developmental processes. In fibroblasts, nuclear movement and shape are controlled by a specific perinuclear actin network made of contractile actin filament bundles called transmembrane actin-associated nuclear (TAN) lines that form a structure called the actin cap. The identification of regulatory proteins associated with this specific actin cytoskeletal dynamic is a priority for understanding actin-based changes in nuclear shape and position in normal and pathological situations. Here, we first identify a unique family of actin regulators, the refilin proteins (RefilinA and RefilinB), that stabilize specifically perinuclear actin filament bundles. We next identify the actin-binding filamin A (FLNA) protein as the downstream effector of refilins. Refilins act as molecular switches to convert FLNA from an actin branching protein into one that bundles. In NIH 3T3 fibroblasts, the RefilinB/FLNA complex organizes the perinuclear actin filament bundles forming the actin cap. Finally, we demonstrate that in epithelial normal murine mammary gland (NmuMG) cells, the RefilinB/FLNA complex controls formation of a new perinuclear actin network that accompanies nuclear shape changes during the epithelial-mesenchymal transition (EMT). Our studies open perspectives for further functional analyses of this unique actin-based network and shed light on FLNA function during development and in human syndromes associated with FLNA mutations.

SUBMITTER: Gay O 

PROVIDER: S-EPMC3136255 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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RefilinB (FAM101B) targets filamin A to organize perinuclear actin networks and regulates nuclear shape.

Gay Olivia O   Gilquin Benoît B   Nakamura Fumihiko F   Jenkins Zandra A ZA   McCartney Rosannah R   Krakow Deborah D   Deshiere Alexandre A   Assard Nicole N   Hartwig John H JH   Robertson Stephen P SP   Baudier Jacques J  

Proceedings of the National Academy of Sciences of the United States of America 20110627 28


The intracellular localization and shape of the nucleus plays a central role in cellular and developmental processes. In fibroblasts, nuclear movement and shape are controlled by a specific perinuclear actin network made of contractile actin filament bundles called transmembrane actin-associated nuclear (TAN) lines that form a structure called the actin cap. The identification of regulatory proteins associated with this specific actin cytoskeletal dynamic is a priority for understanding actin-ba  ...[more]

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