title: Thyroid Hormone-Induced Differentiation of Astrocytes is Associated with Transcriptional Upregulation of β-arrestin-1 and β-adrenergic Receptor-Mediated Endosomal Signaling.
abstract: Thyroid hormones (TH) promote differentiation of astrocytes. We have previously reported that a downstream role β-adrenergic receptor (β-AR) system in such effects of TH. Although evidences indicate strong interaction between TH and the β-ARs, the underlying mechanism is poorly understood. In the present study, we further explored the influence of TH on β-AR signaling during the differentiation process. Unlike β1-AR, binding of (125)I-pindolol to β2-AR in cell membranes was significantly decreased at 2 h of exposure to TH which came back to control values after 24 h. The initial decrease in β2-AR in membranes resulted in a concomitant increase in β2-AR levels in the cytosol, suggesting that TH may induce endocytosis of the receptor. qRT-PCR as well as Western blot analysis demonstrated that unlike β-adrenergic receptor kinase (β-ARK)1 and β-ARK2, the messenger RNA (mRNA) and protein levels of β-arrestin-1 in the astrocyte cultures increased on exposure to TH. Knockdown of β-arrestin gene suggested requirement of both β-arrestin-1 and β-arrestin-2 isoforms during endocytosis of β2-AR, thereby facilitating cell differentiation. Endocytic inhibitors blocked the delayed but sustained activation of p-extracellular signal-regulated kinase (ERK) observed during cell differentiation. Observations suggest that TH upregulate β-arrestin-1 in astrocytes to facilitate endocytosis of β2-AR, required for endosomal ERK activation to drive the differentiation process.
authors.affiliation: Neurobiology Division, Cell Biology & Physiology Department, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India.
authors.forename: Moitreyi
authors.initials: M
authors.lastname: Das
authors.affiliation: Neurobiology Division, Cell Biology & Physiology Department, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India.|Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
authors.forename: Mausam
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: Neurobiology Division, Cell Biology & Physiology Department, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India. sdas@iicb.res.in.
authors.forename: Sumantra
authors.identifier: 0000-0003-2889-8644
authors.initials: S
authors.lastname: Das
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007457:Iodine Radioisotopes; D010766:Phosphorylation / Q000187:drug effects; D010869:Pindolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D000071559:beta-Arrestin 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D011412:Propanolamines; D020033:Protein Isoforms; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D013963:Thyroid Hormones; D000071559:beta-Arrestin 1; C026777:ICI 118551; D010869:Pindolol; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Astrocytes; Endocytosis; Thyroid hormone; siRNA; β-arrestin; β2-adrenergic receptor