Expression and function of the dense-core vesicle membranes are governed by the transcription repressor REST

The membrane of dense-core vesicles is present only in neural cells, where it is instrumental to the regulated discharge of important molecules such as the catecholamine neurotransmitters. The mechanism underlying the specificity of this membrane to certain cell types has so far been unclear. Studies of this problem have been carried out by employing the pheochromocytoma PC12 cell line and its clones defective of dense-core vesicles. REST, the transcription repressor expressed at high levels in non-neural and at very low levels in neural cells, was found to regulate the genes encoding almost all the proteins of both the core and the membrane of the dense-core vesicles, including the transporter for catecholamines and the SNAREs for their exocytosis. Moreover, REST appears to control the assembly of the vesicle membrane. The role of REST in the various steps of the expression and function of the dense-core vesicle membrane is critical during development and participates in the dynamic regulation of mature cell physiology.