PMID- 16179382
OWN - NLM
STAT- MEDLINE
DCOM- 20060518
LR  - 20181201
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 20
IP  - 2
DP  - 2006 Feb
TI  - Differential recruitment of p160 coactivators by glucocorticoid receptor between 
      Schwann cells and astrocytes.
PG  - 254-67
AB  - In the nervous system, glucocorticoids can exert beneficial or noxious effects, 
      depending on their concentration and the duration of hormonal stimulation. They 
      exert their effects on neuronal and glial cells by means of their cognate 
      receptor, the glucocorticoid receptor (GR), which recruits the p160 coactivator 
      family members SRC-1 (steroid receptor coactivator 1), SRC-2, and SRC-3 after 
      hormone binding. In this study, we investigated the molecular pathways used by 
      the GR in cultured glial cells of the central and the peripheral nervous systems, 
      astrocytes and Schwann cells (MSC80 cells), respectively. We performed functional 
      studies based on transient transfection of a minimal glucocorticoid-sensitive 
      reporter gene into the glial cells to test the influence of overexpression or 
      selective inhibition by short interfering RNA of the three p160 coactivator 
      family members on GR transactivation. We demonstrate that, depending on the glial 
      cell type, GR differentially recruits p160 family members: in Schwann cells, GR 
      recruited SRC-1a, SRC-1e, or SRC-3, whereas in astrocytes, SRC-1e and SRC-2, and 
      to a lesser extent SRC-3, were active toward GR signaling. The C-terminal nuclear 
      receptor-interacting domain of SRC-1a participates in its exclusion from the GR 
      transcriptional complex in astrocytes. Immunolocalization experiments revealed a 
      cell-specific intracellular distribution of the p160s, which was dependent on the 
      duration of the hormonal induction. For example, within astrocytes, SRC-1 and 
      SRC-2 were mainly nuclear, whereas SRC-3 unexpectedly localized to the lumen of 
      the Golgi apparatus. In contrast, in Schwann cells, SRC-1 showed a 
      nucleocytoplasmic shuttling depending on hormonal stimulation, whereas SRC-2 
      remained strictly nuclear and SRC-3 remained predominantly cytoplasmic. 
      Altogether, these results highlight the cell specificity and the time dependence 
      of p160s recruitment by the activated GR in glial cells, revealing the complexity 
      of GR-p160 assembly in the nervous system.
FAU - Grenier, Julien
AU  - Grenier J
AD  - Institut National de la Sante et de la Recherche Medicale Unite Mixte de 
      Recherche 488, 80 rue du General Leclerc, 94276 Le Kremlin-Bicetre Cedex, France.
FAU - Trousson, Amalia
AU  - Trousson A
FAU - Chauchereau, Anne
AU  - Chauchereau A
FAU - Cartaud, Jean
AU  - Cartaud J
FAU - Schumacher, Michael
AU  - Schumacher M
FAU - Massaad, Charbel
AU  - Massaad C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050922
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (Nuclear Receptor Interacting Protein 1)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Ncoa3 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 3)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Astrocytes/chemistry/*metabolism
MH  - Cell Nucleus/chemistry
MH  - Cytoplasm/chemistry
MH  - Genes, Reporter
MH  - Histone Acetyltransferases
MH  - Mice
MH  - Nuclear Proteins/genetics/metabolism
MH  - Nuclear Receptor Coactivator 1
MH  - Nuclear Receptor Coactivator 2/analysis/antagonists & inhibitors/*metabolism
MH  - Nuclear Receptor Coactivator 3
MH  - Nuclear Receptor Interacting Protein 1
MH  - Protein Structure, Tertiary
MH  - RNA, Small Interfering/genetics/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glucocorticoid/genetics/*metabolism
MH  - Schwann Cells/chemistry/*metabolism
MH  - Trans-Activators/analysis/antagonists & inhibitors/*metabolism
MH  - Transcription Factors/analysis/antagonists & inhibitors/*metabolism
MH  - Transcriptional Activation
EDAT- 2005/09/24 09:00
MHDA- 2006/05/19 09:00
CRDT- 2005/09/24 09:00
PHST- 2005/09/24 09:00 [pubmed]
PHST- 2006/05/19 09:00 [medline]
PHST- 2005/09/24 09:00 [entrez]
AID - me.2005-0061 [pii]
AID - 10.1210/me.2005-0061 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2006 Feb;20(2):254-67. doi: 10.1210/me.2005-0061. Epub 2005 Sep 
      22.