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

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.

journal_name

Ann N Y Acad Sci

authors

D'Alessandro R,Klajn A,Meldolesi J

doi

10.1111/j.1749-6632.2008.03988.x

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

194-200

eissn

0077-8923

issn

1749-6632

pii

NYAS03988

journal_volume

1152

pub_type

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