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

Keywords

  • Chromogranin
  • Histone deacetylase
  • PC12
  • SNARE
  • Transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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