Expression of the neurosecretory process in pc12 cells is governed by rest
2008
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Authors
D'Alessandro, RosalbaLazić, Andrijana
Stucchi, Laura
Podini, Paola
Malosio, Maria Luisa
Meldolesi, Jacopo
Article (Published version)
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The neurosecretory process is acquired during differentiation and can be lost en block by differentiated cells. To investigate the role of REST/NRSF, a transcription repressor, in the maintenance of the process we studied two PC12 clones, one wt and one defective, expressing low and high levels of endogenous RE-1 silencing transcription (factor) (REST), respectively. Stable transfection of constructs demonstrated that REST represses 10 genes coding for proteins of neurosecretory vesicles and their exocytosis, eight including and two lacking the REST-binding sequence, RE-1. Of these genes, those of chromogranins were strongly repressed by fewfold increases of REST, those of VAMP2 and syntaxin1a required much higher levels. Moreover, in wt cells transfected with an active construct the dense-core vesicles, still competent for regulated exocytosis, were much smaller, with lighter cores; in defective cells, the dominant-negative construct induced the rescue of many vesicle/exocytosis genes... but not of those of chromogranins. Small dense-core vesicles, exocytized upon stimulation, were rescued when the construct-transfected defective cells were transfected also with chromograninA or treated with trichostatinA, a blocker of histone deacetylases. Our results identify REST, working by direct and indirect mechanisms, as the factor governing the maintenance of the neurosecretory process and the properties of dense-core vesicles in PC12 cells.
Keywords:
SNAREs / regulated exocytosis / gene expression / dense-core vesicle / chromograninsSource:
Journal of Neurochemistry, 2008, 105, 4, 1369-1383Publisher:
- Blackwell Publishing, Oxford
DOI: 10.1111/j.1471-4159.2008.05259.x
ISSN: 0022-3042
PubMed: 18298477
WoS: 000255286600027
Scopus: 2-s2.0-42549096459
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - D'Alessandro, Rosalba AU - Lazić, Andrijana AU - Stucchi, Laura AU - Podini, Paola AU - Malosio, Maria Luisa AU - Meldolesi, Jacopo PY - 2008 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/336 AB - The neurosecretory process is acquired during differentiation and can be lost en block by differentiated cells. To investigate the role of REST/NRSF, a transcription repressor, in the maintenance of the process we studied two PC12 clones, one wt and one defective, expressing low and high levels of endogenous RE-1 silencing transcription (factor) (REST), respectively. Stable transfection of constructs demonstrated that REST represses 10 genes coding for proteins of neurosecretory vesicles and their exocytosis, eight including and two lacking the REST-binding sequence, RE-1. Of these genes, those of chromogranins were strongly repressed by fewfold increases of REST, those of VAMP2 and syntaxin1a required much higher levels. Moreover, in wt cells transfected with an active construct the dense-core vesicles, still competent for regulated exocytosis, were much smaller, with lighter cores; in defective cells, the dominant-negative construct induced the rescue of many vesicle/exocytosis genes but not of those of chromogranins. Small dense-core vesicles, exocytized upon stimulation, were rescued when the construct-transfected defective cells were transfected also with chromograninA or treated with trichostatinA, a blocker of histone deacetylases. Our results identify REST, working by direct and indirect mechanisms, as the factor governing the maintenance of the neurosecretory process and the properties of dense-core vesicles in PC12 cells. PB - Blackwell Publishing, Oxford T2 - Journal of Neurochemistry T1 - Expression of the neurosecretory process in pc12 cells is governed by rest EP - 1383 IS - 4 SP - 1369 VL - 105 DO - 10.1111/j.1471-4159.2008.05259.x ER -
@article{ author = "D'Alessandro, Rosalba and Lazić, Andrijana and Stucchi, Laura and Podini, Paola and Malosio, Maria Luisa and Meldolesi, Jacopo", year = "2008", abstract = "The neurosecretory process is acquired during differentiation and can be lost en block by differentiated cells. To investigate the role of REST/NRSF, a transcription repressor, in the maintenance of the process we studied two PC12 clones, one wt and one defective, expressing low and high levels of endogenous RE-1 silencing transcription (factor) (REST), respectively. Stable transfection of constructs demonstrated that REST represses 10 genes coding for proteins of neurosecretory vesicles and their exocytosis, eight including and two lacking the REST-binding sequence, RE-1. Of these genes, those of chromogranins were strongly repressed by fewfold increases of REST, those of VAMP2 and syntaxin1a required much higher levels. Moreover, in wt cells transfected with an active construct the dense-core vesicles, still competent for regulated exocytosis, were much smaller, with lighter cores; in defective cells, the dominant-negative construct induced the rescue of many vesicle/exocytosis genes but not of those of chromogranins. Small dense-core vesicles, exocytized upon stimulation, were rescued when the construct-transfected defective cells were transfected also with chromograninA or treated with trichostatinA, a blocker of histone deacetylases. Our results identify REST, working by direct and indirect mechanisms, as the factor governing the maintenance of the neurosecretory process and the properties of dense-core vesicles in PC12 cells.", publisher = "Blackwell Publishing, Oxford", journal = "Journal of Neurochemistry", title = "Expression of the neurosecretory process in pc12 cells is governed by rest", pages = "1383-1369", number = "4", volume = "105", doi = "10.1111/j.1471-4159.2008.05259.x" }
D'Alessandro, R., Lazić, A., Stucchi, L., Podini, P., Malosio, M. L.,& Meldolesi, J.. (2008). Expression of the neurosecretory process in pc12 cells is governed by rest. in Journal of Neurochemistry Blackwell Publishing, Oxford., 105(4), 1369-1383. https://doi.org/10.1111/j.1471-4159.2008.05259.x
D'Alessandro R, Lazić A, Stucchi L, Podini P, Malosio ML, Meldolesi J. Expression of the neurosecretory process in pc12 cells is governed by rest. in Journal of Neurochemistry. 2008;105(4):1369-1383. doi:10.1111/j.1471-4159.2008.05259.x .
D'Alessandro, Rosalba, Lazić, Andrijana, Stucchi, Laura, Podini, Paola, Malosio, Maria Luisa, Meldolesi, Jacopo, "Expression of the neurosecretory process in pc12 cells is governed by rest" in Journal of Neurochemistry, 105, no. 4 (2008):1369-1383, https://doi.org/10.1111/j.1471-4159.2008.05259.x . .