Molecular and Cell Biology of Lipids
In spite of the encouraging results obtained in experimental models, the clinical use of regeneration therapies based on stem cells is hampered by the lack of knowledge about the molecular mechanisms that govern tissue regeneration from adult stem cells in vivo or cell differentiation. Therefore, the characterizations of the biology of stem cells and of the mechanisms that underlie the process of differentiation of particular cell types are a pre-requisite for the development of therapeutic strategies. Moreover, the hypothesis that errant growth of NSCs could give rise to brain tumors makes it even more compelling to investigate the biology of these cells, specially the role of molecules that regulate cell fate.
Several lines of evidence support the notion that phospholipids play several essential roles during neuronal differentiation. Phospholipids not only play a structural function in biological membranes and therefore are required to face the augmented demand for new membrane biosynthesis during neuronal differentiation but also are important signaling molecules regulating neuronal
differentiation. Towards this goal, we are directing our research efforts towards understanding the mechanism by which phospholipids metabolism promotes neuronal differentiation using neuronal cell lines and stem cells as a model specially the role of molecules that regulate cell fate.
Phospholipids and its role during neuronal differentiation.
Little progress has been made in understanding neuronal membrane biogenesis in the context of differentiation. We are directing our research efforts towards understanding how cells manage to create enough new membrane PtdCho to support neurite formation during differentiation. Towards this goal, we recently found that RA-induced differentiation of neuroblastoma cells was characterized by increased PtdCho biosynthesis mediated by increased in the expression of two key enzymes. We propose that the transcripts encoding these two enzymes of the PtdCho-biosynthetic pathway are stimulated in a coordinate manner to optimize membrane PtdCho formation. The specific questions we want to answer in this project are: What mechanism is common to the stimulation of both PtdCho-biosynthetic genes during RA-induced neuronal differentiation? Is this mechanism common for other genes whose expression is stimulated during neuritogenesis?
- Paoletti L, Domizi P, Marcucci H, Montaner A, Krapf D, Salvador G, Banchio C. Lysophosphatidylcholine Drives Neuroblast Cell Fate. Mol Neurobiol. 2016 Nov;53(9):6316-6331.
- David, A.P, Margarit, E, Domizi, P, Banchio, C. E, Armas, P (Co-corresponding author), Calcaterra, N.B. G-quadruplexes as novel cis-elements controlling transcription during embryonic development". Nucleic Acids Res. 44(9): 4163–4173. DOI: 10.1093/nar/gkw011; (2016)
- Paoletti, L. Domizi, P, Marcucci, H., Montaner, A., Krapf D, Salvador G. and Banchio C. Lisophosphatidylcholine drives neuroblastcellfate”. Mol Neurobiol. (2015).
- Domizi P, Aoyama and Banchio C. (2014) Choline Kinase alpha Expression during RA-induced Neuronal Differentiation: role of C/EBPb. BBA - Molecular and Cell Biology of Lipids, 1841, 544-55.
- Paoletti L, Elena C, Domizi P, Banchio C (2011) Role of phosphatidylcholine during neuronal differentiation. IUBMB Life, 63, 714-20.
- Marcucci, H, Paoletti, L. Jackowski S, Banchio C. (2010) Phosphatidylcholine biosíntesis and its role in neuronal cell fate determination. J Biol Chem., 285:25382-25393.
- Elena C, Banchio C. (2010) Specific interaction between E2F1 and Sp1 regulates the expression of murine CTP:phosphocholine cytidylyltransferase alpha during the S phase. Biochim Biophys Acta, 1801, 537-546.
- Marcucci, H, Elena, C, Gilardoni, P. Banchio C. (2008) Characterization of the Murine CTP:Phosphocholine Cytidylyltransferase beta Gene Promoter. BBA - Molecular and Cell Biology of Lipids, 1781, 254-62.
- Sugimoto, H, Banchio, C, Vance D.E. (2008) Transcriptional regulation of phosphatidylcholine biosynthesis. Prog. Lipid Res., 47, 204-20.
- Banchio, C. Lingrell S, Vance D. (2007) Sp-1 binds promoter elements regulated by Rb and regulates CTP:phosphocholine cytidylyltransferase alpha transcription. J Biol Chem., 282, 14827-35.
- Banchio, C., Lingrell S., Vance DE. (2006) Role of histone deacetylase in the expression of CTP: Phosphocholine cytidylyltransferase alpha (CTalpha). J. Biol. Chem., 281, 10010-5.
- Banchio, C., Shang, L. Vance, D.E. (2004) Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates its role in CT regulation during the S phase of the cell cycle. J Biol Chem., 279, 40220-6
- Banchio, C., Shang, L. Vance, D.E. (2003) Activation of CTP: Phosphocholine cytidylyltransferase alpha expression during the S phase of the cell cycle is mediated by the transcription factor Sp1. J Biol Chem., 278, 32457-64.
- Dr Marcos Costa (UFRN Natal Brasil).
- PICT 2013-0820 “Fosfatidilcolina como estímulo de la diferenciación neuronal. Mecanismos moleculares subyacentes e impacto en la diferenciación”.
- PICT 2015-0123 Lípidos como reguladores del destino de células madre neuronales. Mecanismos moleculares subyacentes e impacto en la regeneración.
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Detección de bIII-tubulina (verde) por inmunocitoquímica en células Neuro-2a que expresan constitutivamente CCTa.