title: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 873, F-38054 Grenoble, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Gay
authors.forename: Benoît
authors.initials: B
authors.lastname: Gilquin
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakamura
authors.forename: Zandra A
authors.initials: ZA
authors.lastname: Jenkins
authors.forename: Rosannah
authors.initials: R
authors.lastname: McCartney
authors.forename: Deborah
authors.initials: D
authors.lastname: Krakow
authors.forename: Alexandre
authors.initials: A
authors.lastname: Deshiere
authors.forename: Nicole
authors.initials: N
authors.lastname: Assard
authors.forename: John H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Robertson
authors.forename: Jacques
authors.initials: J
authors.lastname: Baudier
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001254:Astrocytoma / Q000378:metabolism / Q000648:ultrastructure; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D003285:Contractile Proteins / Q000378:metabolism*; D019281:Dimerization; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D064448:Filamins; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D041681:NIH 3T3 Cells; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D000199:Actins; D002352:Carrier Proteins; D003285:Contractile Proteins; C034037:F-actin-binding proteins; D064448:Filamins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering