J Biol Chem, Vol. 273, Issue 52, 34683-34686, December 25, 1998

COMMUNICATION
Neurosecretion Competence, an Independently Regulated Trait of the Neurosecretory Cell Phenotype

Barbara Borgonovo, Gabriella Racchetti, MariaLuisa Malosio, Roberta Benfante, Paola Podini, Patrizia Rosa^§, and Jacopo Meldolesi^§

From the  DIBIT, Department of Neurosciences, San Raffaele Scientific Institute and B. Ceccarelli Center, Department of Pharmacology, University of Milan, 20132 Milan, Italy and the ^§ Consiglio Nazionale Ricerche Center of Molecular and Cellular Pharmacology, University of Milan, 20129 Milan, Italy

Neurosecretion competence is intended as the ability of neurosecretory cells to express dense and clear vesicles discharged by regulated exocytosis (neurotransmitter release). Such a property, which so far has never been studied independently, is investigated here by a heterotypic cell fusion approach, using a clone of rat pheochromocytoma PC12 cells totally incompetent for neurosecretion that still largely maintains its typical molecular and cellular phenotype. When fused with wild-type partners of various species (rat, human) and specialization (PC12, neuroblastoma SH-SY5Y, HeLa), the defective cells reacquire their competence as revealed by the expression of their secretion-specific proteins. Fused wild-type cells therefore appear able to complement defective cells by providing them with factor(s) inducing the reactivation of their secretory program. The mechanism of action of these factors may consist not in a coordinate unblocking of transcription but in the prevention of a rapid post-transcriptional degradation of the mRNAs for secretion-specific genes.