PMID- 24658146
OWN - NLM
STAT- MEDLINE
DCOM- 20150116
LR  - 20231213
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 3
DP  - 2014
TI  - Subcellular fractionation and localization studies reveal a direct interaction of 
      the fragile X mental retardation protein (FMRP) with nucleolin.
PG  - e91465
LID - 10.1371/journal.pone.0091465 [doi]
LID - e91465
AB  - Fragile X mental Retardation Protein (FMRP) is a well-known regulator of local 
      translation of its mRNA targets in neurons. However, despite its ubiquitous 
      expression, the role of FMRP remains ill-defined in other cell types. In this 
      study we investigated the subcellular distribution of FMRP and its protein 
      complexes in HeLa cells using confocal imaging as well as detergent-free 
      fractionation and size exclusion protocols. We found FMRP localized exclusively 
      to solid compartments, including cytosolic heavy and light membranes, 
      mitochondria, nuclear membrane and nucleoli. Interestingly, FMRP was associated 
      with nucleolin in both a high molecular weight ribosomal and 
      translation-associated complex (>/=6 MDa) in the cytosol, and a low molecular 
      weight complex ( approximately 200 kDa) in the nucleoli. Consistently, we identified two 
      functional nucleolar localization signals (NoLSs) in FMRP that are responsible 
      for a strong nucleolar colocalization of the C-terminus of FMRP with nucleolin, 
      and a direct interaction of the N-terminus of FMRP with the 
      arginine-glycine-glycine (RGG) domain of nucleolin. Taken together, we propose a 
      novel mechanism by which a transient nucleolar localization of FMRP underlies a 
      strong nucleocytoplasmic translocation, most likely in a complex with nucleolin 
      and possibly ribosomes, in order to regulate translation of its target mRNAs.
FAU - Taha, Mohamed S
AU  - Taha MS
AD  - Institute of Biochemistry and Molecular Biology II, Medical Faculty of the 
      Heinrich-Heine-University, Dusseldorf, Germany.
FAU - Nouri, Kazem
AU  - Nouri K
AD  - Institute of Biochemistry and Molecular Biology II, Medical Faculty of the 
      Heinrich-Heine-University, Dusseldorf, Germany.
FAU - Milroy, Lech G
AU  - Milroy LG
AD  - Laboratory of Chemical Biology and Institute of Complex Molecular Systems, 
      Department of Biomedical Engineering, Technische Universiteit Eindhoven, 
      Eindhoven, the Netherlands.
FAU - Moll, Jens M
AU  - Moll JM
AD  - Institute of Biochemistry and Molecular Biology II, Medical Faculty of the 
      Heinrich-Heine-University, Dusseldorf, Germany.
FAU - Herrmann, Christian
AU  - Herrmann C
AD  - Department of Physical Chemistry I, Ruhr University Bochum, Bochum, Germany.
FAU - Brunsveld, Luc
AU  - Brunsveld L
AD  - Laboratory of Chemical Biology and Institute of Complex Molecular Systems, 
      Department of Biomedical Engineering, Technische Universiteit Eindhoven, 
      Eindhoven, the Netherlands.
FAU - Piekorz, Roland P
AU  - Piekorz RP
AD  - Institute of Biochemistry and Molecular Biology II, Medical Faculty of the 
      Heinrich-Heine-University, Dusseldorf, Germany.
FAU - Ahmadian, Mohammad R
AU  - Ahmadian MR
AD  - Institute of Biochemistry and Molecular Biology II, Medical Faculty of the 
      Heinrich-Heine-University, Dusseldorf, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140321
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
SB  - IM
MH  - Cell Fractionation
MH  - Fragile X Mental Retardation Protein/analysis/*metabolism
MH  - Gene Expression Regulation
MH  - HeLa Cells
MH  - Humans
MH  - Nuclear Localization Signals
MH  - Phosphoproteins/analysis/*metabolism
MH  - Protein Transport
MH  - RNA, Messenger/metabolism
MH  - RNA-Binding Proteins/analysis/*metabolism
MH  - Nucleolin
PMC - PMC3962360
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/03/25 06:00
MHDA- 2015/01/17 06:00
PMCR- 2014/03/21
CRDT- 2014/03/25 06:00
PHST- 2013/11/10 00:00 [received]
PHST- 2014/02/11 00:00 [accepted]
PHST- 2014/03/25 06:00 [entrez]
PHST- 2014/03/25 06:00 [pubmed]
PHST- 2015/01/17 06:00 [medline]
PHST- 2014/03/21 00:00 [pmc-release]
AID - PONE-D-13-47208 [pii]
AID - 10.1371/journal.pone.0091465 [doi]
PST - epublish
SO  - PLoS One. 2014 Mar 21;9(3):e91465. doi: 10.1371/journal.pone.0091465. eCollection 
      2014.