GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:21709252

From GONUTS
Jump to: navigation, search
Citation

Gay, O, Gilquin, B, Nakamura, F, Jenkins, ZA, McCartney, R, Krakow, D, Deshiere, A, Assard, N, Hartwig, JH, Robertson, SP and Baudier, J (2011) RefilinB (FAM101B) targets filamin A to organize perinuclear actin networks and regulates nuclear shape. Proc. Natl. Acad. Sci. U.S.A. 108:11464-9

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.

Links

PubMed PMC3136255 Online version:10.1073/pnas.1104211108

Keywords

Actins/metabolism; Amino Acid Sequence; Animals; Astrocytoma/metabolism; Astrocytoma/ultrastructure; Base Sequence; Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Cell Line, Tumor; Cell Nucleus/metabolism; Cell Nucleus/ultrastructure; Contractile Proteins/metabolism; Dimerization; Epithelial-Mesenchymal Transition; Female; Humans; Mammary Glands, Animal/cytology; Mammary Glands, Animal/metabolism; Mice; Microfilament Proteins/chemistry; Microfilament Proteins/genetics; Microfilament Proteins/metabolism; Microscopy, Electron, Transmission; Molecular Sequence Data; Multiprotein Complexes; NIH 3T3 Cells; Protein Interaction Domains and Motifs; RNA, Small Interfering/genetics; Sequence Deletion

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RFLB

acts_upstream_of_or_within

GO:0030036: actin cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RFLB

acts_upstream_of_or_within

GO:0030036: actin cytoskeleton organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95556

P

Seeded From UniProt

complete

MOUSE:RFLB

acts_upstream_of_or_within

GO:0001837: epithelial to mesenchymal transition

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95556

P

Seeded From UniProt

complete

MOUSE:RFLB

located_in

GO:0015629: actin cytoskeleton

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RFLB

enables

GO:0031005: filamin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FLNA

acts_upstream_of_or_within

GO:0030036: actin cytoskeleton organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1923816

P

Seeded From UniProt

complete

MOUSE:FLNA

acts_upstream_of_or_within

GO:0001837: epithelial to mesenchymal transition

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1923816

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.