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Expression of Dense‐core Vesicles and of Their Exocytosis Are Governed by the Repressive Transcription Factor NRSF/REST
Author(s) -
D'Alessandro Rosalba,
Klajn Andrijana,
Meldolesi Jacopo
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2008.03988.x
Subject(s) - exocytosis , repressor , microbiology and biotechnology , vesicle , biology , transcription factor , gene silencing , chemistry , secretion , gene , genetics , biochemistry , membrane
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.