Nuclear lipid microdomains regulate nuclear vitamin D3 uptake and influence embryonic hippocampal cell differentiation
Bartoccini, Elisa ; Marini, Francesca ; Damaskopoulou, Eleni ; et al. ; - ASI Sponsor
Sep - 2011
DOI: 10.1091/mbc.E11-03-0196
ISSN : 1939-4586 ;
journal : Molecular biology of the cell

Volume : 22 ; Issue : 17
type: Article Journal

Despite recent advances in the understanding of the role of 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) in the CNS, the mechanism of action remains obscure. We demonstrate that some 1,25-(OH)(2)D(3) receptor (VDR) is localized in the cell nucleus in specialized microdomains enriched in sphingomyelin and cholesterol; the integrity of these microdomains is necessary for embryonic hippocampal cell differentiation. Sphingomyelinase (SMase) treatment reduces both VDR and labeled 1,25-(OH)(2)D(3) content in nuclear microdomains. We have previously shown that HN9.10e embryonic hippocampal cells differentiate when incubated with 100 nM 1,25-(OH)(2)D(3) in the presence of 10\% fetal calf serum, while serum deprivation induces cell death. In this study, we have investigated whether conditions that alter lipid content of nuclear microdomains modify 1,25-(OH)(2)D(3)-induced differentiation. Serum deprivation activates SMase and modifies the composition of nuclear microdomains, which lose the 1,25-(OH)(2) vitamin D(3) receptor. The incubation of serum-deprived cells with 100 nM 1,25-(OH)(2)D(3) prevents differentiation. However, treatment with 400 nM 1,25-(OH)(2)D(3) during serum withdrawal increases the lipid content of the nuclear microdomains, allows the interaction of 1,25-(OH)(2)D(3) with its receptor, and results in differentiation. These results suggest the presence of VDR in nuclear microdomains is necessary for 1,25-(OH)(2)D(3)-induced differentiation in embryonic hippocampal cells.

keywords : Animals,Calcitriol,Calcitriol: metabolism,Cell Differentiation,Cell Line,Cell Nucleus,Cell Nucleus: metabolism,Cell Shape,Cholecalciferol,Cholecalciferol: pharmacology,Cholecalciferol: physiology,Hippocampus,Hippocampus: cytology,Hippocampus: embryology,Hippocampus: metabolism,Lipid Metabolism,Membrane Microdomains,Membrane Microdomains: metabolism,Mice,Nerve Growth Factor,Nerve Growth Factor: metabolism,Nuclear Envelope,Nuclear Envelope: metabolism,Proto-Oncogene Proteins,Proto-Oncogene Proteins: metabolism,Receptors,Sphingomyelin Phosphodiesterase,Sphingomyelin Phosphodiesterase: pharmacology,Sphingomyelin Phosphodiesterase: physiology,Sphingomyelins,Sphingomyelins: metabolism