Expression of dense-core vesicles and of their exocytosis are governed by the repressive transcription factor NRSF/REST

Rosalba D'Alessandro, Andrijana Klajn, Jacopo Meldolesi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The mechanism by which neurons and neurosecretory cells govern the expression and the exocytic discharge of their clear and dense-core vesicles had remained unclear until recently when studies in the neurosecretory cell model PC12 revealed these processes to be orchestrated by the transcriptional repressor neuron restrictive silencer factor (NRSF)/repressor element-1 silencing transcription factor (REST). In wild-type PC12 fully competent for neurosecretion, NRSF/REST is low. The genes of the proteins involved in neurosecretion [from the secretory to vesicle membrane and plasma membrane proteins, including the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) of exocytosis] were all repressed by increases of NRSF/REST expression to various extents when the increase was only a fewfold but were completely or almost completely repressed when the increase was large, as in spontaneously defective PC12 clones. In the first case the dense-core vesicles were still competent for exocytosis but were smaller and less dense than in wild-type cells; in the second they were no longer visible but did reappear when the repression was attenuated by transfection of a dominant-negative construct of NRSF/REST combined with a secretory chromogranin or strengthened by treatment with a blocker of NRSF/REST-associated enzymes, the histone deacetylases.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages194-200
Number of pages7
Volume1152
DOIs
Publication statusPublished - Jan 2009

Publication series

NameAnnals of the New York Academy of Sciences
Volume1152
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Transcriptional Silencer Elements
Exocytosis
Secretory Vesicles
Transcription Factors
Neurosecretion
Chromogranins
SNARE Proteins
Histone Deacetylases
PC12 Cells
Cell membranes
Neurons
Transfection
Blood Proteins
Membrane Proteins
Clone Cells
Cell Membrane
RE1-silencing transcription factor
Membranes
Enzymes
Proteins

Keywords

  • Chromogranin
  • Histone deacetylase
  • PC12
  • SNARE
  • Transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

D'Alessandro, R., Klajn, A., & Meldolesi, J. (2009). Expression of dense-core vesicles and of their exocytosis are governed by the repressive transcription factor NRSF/REST. In Annals of the New York Academy of Sciences (Vol. 1152, pp. 194-200). (Annals of the New York Academy of Sciences; Vol. 1152). https://doi.org/10.1111/j.1749-6632.2008.03988.x

Expression of dense-core vesicles and of their exocytosis are governed by the repressive transcription factor NRSF/REST. / D'Alessandro, Rosalba; Klajn, Andrijana; Meldolesi, Jacopo.

Annals of the New York Academy of Sciences. Vol. 1152 2009. p. 194-200 (Annals of the New York Academy of Sciences; Vol. 1152).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

D'Alessandro, R, Klajn, A & Meldolesi, J 2009, Expression of dense-core vesicles and of their exocytosis are governed by the repressive transcription factor NRSF/REST. in Annals of the New York Academy of Sciences. vol. 1152, Annals of the New York Academy of Sciences, vol. 1152, pp. 194-200. https://doi.org/10.1111/j.1749-6632.2008.03988.x
D'Alessandro R, Klajn A, Meldolesi J. Expression of dense-core vesicles and of their exocytosis are governed by the repressive transcription factor NRSF/REST. In Annals of the New York Academy of Sciences. Vol. 1152. 2009. p. 194-200. (Annals of the New York Academy of Sciences). https://doi.org/10.1111/j.1749-6632.2008.03988.x
D'Alessandro, Rosalba ; Klajn, Andrijana ; Meldolesi, Jacopo. / Expression of dense-core vesicles and of their exocytosis are governed by the repressive transcription factor NRSF/REST. Annals of the New York Academy of Sciences. Vol. 1152 2009. pp. 194-200 (Annals of the New York Academy of Sciences).
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