Expression of dense-core vesicles and of their exocytosis are governed by the repressive transcription factor NRSF/REST.
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.
D'Alessandro
Rosalba
R
Vita-Salute San Raffaele University, Milan, Italy.
Klajn
Andrijana
A
Meldolesi
Jacopo
J
D000818:Animals; D002454:Cell Differentiation; D005089:Exocytosis; D007425:Intracellular Membranes / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor