Spatial control of nucleoporin condensation by fragile X-related proteins.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_F93EA3DA3D5C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Spatial control of nucleoporin condensation by fragile X-related proteins.
Journal
The EMBO journal
Author(s)
Agote-Aran A., Schmucker S., Jerabkova K., Jmel Boyer I., Berto A., Pacini L., Ronchi P., Kleiss C., Guerard L., Schwab Y., Moine H., Mandel J.L., Jacquemont S., Bagni C., Sumara I.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Publication state
Published
Issued date
15/10/2020
Peer-reviewed
Oui
Volume
39
Number
20
Pages
e104467
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Nucleoporins (Nups) build highly organized nuclear pore complexes (NPCs) at the nuclear envelope (NE). Several Nups assemble into a sieve-like hydrogel within the central channel of the NPCs. In the cytoplasm, the soluble Nups exist, but how their assembly is restricted to the NE is currently unknown. Here, we show that fragile X-related protein 1 (FXR1) can interact with several Nups and facilitate their localization to the NE during interphase through a microtubule-dependent mechanism. Downregulation of FXR1 or closely related orthologs FXR2 and fragile X mental retardation protein (FMRP) leads to the accumulation of cytoplasmic Nup condensates. Likewise, models of fragile X syndrome (FXS), characterized by a loss of FMRP, accumulate Nup granules. The Nup granule-containing cells show defects in protein export, nuclear morphology and cell cycle progression. Our results reveal an unexpected role for the FXR protein family in the spatial regulation of nucleoporin condensation.
Keywords
Acrylates/pharmacology, Animals, Cell Line, Cell Nucleus/metabolism, Cytoplasm/drug effects, Cytoplasm/metabolism, Down-Regulation, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Fragile X Syndrome/genetics, Fragile X Syndrome/metabolism, G1 Phase Cell Cycle Checkpoints/genetics, Humans, In Situ Hybridization, Fluorescence, Interphase/genetics, Mice, Microscopy, Electron, Transmission, Microtubules/drug effects, Microtubules/metabolism, Microtubules/ultrastructure, Myoblasts/drug effects, Myoblasts/metabolism, Nuclear Envelope/drug effects, Nuclear Envelope/metabolism, Nuclear Envelope/ultrastructure, Nuclear Pore Complex Proteins/genetics, Nuclear Pore Complex Proteins/metabolism, RNA, Small Interfering, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism, FXR1, dynein, fragile X syndrome, nucleoporins, phase separation
Pubmed
Web of science
Open Access
Yes
Create date
11/08/2020 10:49
Last modification date
25/01/2024 7:47
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