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Cocaine hijacks sigma‐1 receptors from the ER to the nuclear membrane to interact with lamina A/C: Effect on MeCP2 gene expression
Author(s) -
Chuang Chien-Ying,
Tsai Shang-Yi,
Hayashi Teruo,
Hung Jan-Jong,
Chang Wen-Chang,
Su Tsung-Ping
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb582
Subject(s) - lamin , nuclear lamina , microbiology and biotechnology , nuclear membrane , biology , mecp2 , chemistry , nucleus , transcription factor , gene , genetics , nuclear protein , phenotype
The sigma‐1 receptor (Sig‐1R) is an endoplasmic reticulum (ER)‐resident non‐opioid receptor that is expressed in the nervous system and can regulate cellular differentiation, neuroplasticity, and neuroprotection. Nuclear lamins in the nucleus are essential for the nuclear envelope assembly, DNA synthesis, and gene transcription. We tested here the hypothesis that cocaine, via Sig‐1Rs, may affect the gene expression of methyl CpG binding protein 2 (MeCP2) which relates to cocaine addiction. In glial and NG108‐15 cells, cocaine increases the nuclear envelope invaginations (NEI) and grooving, suggesting that the nuclear‐cytoplasmic exchange is enhanced by cocaine. Confocal microscopic data show that cocaine and another Sig‐1R agonist DHEAS cause the translocation of Sig‐1Rs from the ER into the nuclear membrane. After cocaine treatment, Sig‐1Rs localize mainly in the outer membrane of the nucleus and could increase the chance to interact with lamin A/C. Cocaine is known to cause addictive behavior by upregulating (MeCP2) in the brain. In rat primary cortical neurons, cocaine causes an increase in MeCP2. This effect is antagonized by Sig‐1R antagonist BD1063. Our results suggest that cocaine increases MeCP2 gene expression by translocating Sig‐1Rs into the nuclear outer membrane to increase the NEI and grooving to facilitate the Sig‐1R‐lamin A/C interaction to regulate the MeCP2 gene expression.