Rab1b overexpression modifies Golgi size and gene expression in HeLa cells and modulates the thyrotrophin response in thyroid cells in culture – ScienceOpen
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      Rab1b overexpression modifies Golgi size and gene expression in HeLa cells and modulates the thyrotrophin response in thyroid cells in culture

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          Abstract

          An increase in Rab1b levels induces changes in Golgi size and in gene expression. These Rab1b-dependent changes require the activity of p38 mitogen-activated protein kinase and the cAMP-responsive element binding protein consensus binding. The results show a Rab1b increase in secretory cells after stimulation and suggest that this increase is required to elicit a secretory response.

          Abstract

          Rab1b belongs to the Rab-GTPase family that regulates membrane trafficking and signal transduction systems able to control diverse cellular activities, including gene expression. Rab1b is essential for endoplasmic reticulum–Golgi transport. Although it is ubiquitously expressed, its mRNA levels vary among different tissues. This work aims to characterize the role of the high Rab1b levels detected in some secretory tissues. We report that, in HeLa cells, an increase in Rab1b levels induces changes in Golgi size and gene expression. Significantly, analyses applied to selected genes, KDELR3, GM130 (involved in membrane transport), and the proto-oncogene JUN, indicate that the Rab1b increase acts as a molecular switch to control the expression of these genes at the transcriptional level, resulting in changes at the protein level. These Rab1b-dependent changes require the activity of p38 mitogen-activated protein kinase and the cAMP-responsive element-binding protein consensus binding site in those target promoter regions. Moreover, our results reveal that, in a secretory thyroid cell line (FRTL5), Rab1b expression increases in response to thyroid-stimulating hormone (TSH). Additionally, changes in Rab1b expression in FRTL5 cells modify the specific TSH response. Our results show, for the first time, that changes in Rab1b levels modulate gene transcription and strongly suggest that a Rab1b increase is required to elicit a secretory response.

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          Author and article information

          Contributors
          Role: Monitoring Editor
          Journal
          Mol Biol Cell
          Mol. Biol. Cell
          molbiolcell
          mbc
          Mol. Bio. Cell
          Molecular Biology of the Cell
          The American Society for Cell Biology
          1059-1524
          1939-4586
          01 March 2013
          : 24
          : 5
          : 617-632
          Affiliations
          [1] aCentro de Investigaciones en Bioquímica Clínica e Inmunología, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
          [2] bDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298
          [3] cIFOM Foundation, FIRC Institute of Molecular Oncology, 20139 Milan, Italy
          [4] dTelethon Institute of Genetics and Medicine, Naples 80131, Italy
          Carnegie Mellon University
          Author notes
          1Address correspondence to: Cecilia Alvarez ( cequila@ 123456hotmail.com ).
          Article
          E12-07-0530
          10.1091/mbc.E12-07-0530
          3583665
          23325787
          e95e0517-9af9-4e97-900f-85384f8b71e8
          © 2013 Romero et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License ( http://creativecommons.org/licenses/by-nc-sa/3.0).

          “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.

          History
          : 18 July 2012
          : 19 December 2012
          : 07 January 2013
          Categories
          Articles
          Membrane Trafficking
          A Highlights from MBoC Selection

          Molecular biology
          Molecular biology

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