Lippincott Williams & Wilkins, Inc., Philadelphia
Cyclic AMP-Responsive Element Binding Protein in Brain Mitochondria
Article first published online: 18 JAN 2002
Journal of Neurochemistry
Volume 72, Issue 6, pages 2272–2277, June 1999
How to Cite
Cammarota, M., Paratcha, G., Bevilaqua, L. R. M., De Stein, M. L., Lopez, M., De Iraldi, A. P., Izquierdo, I. and Medina, J. H. (1999), Cyclic AMP-Responsive Element Binding Protein in Brain Mitochondria. Journal of Neurochemistry, 72: 2272–2277. doi: 10.1046/j.1471-4159.1999.0722272.x
Drs. G. Paratcha and L. R. M. Bevilaqua contributed equally to the work and could be cited in interchangeable order.
Abbreviations used: CA-CRE, calcium—cyclic AMP-responsive element; αCAMKII, α-Ca2+/calmodulin-dependent kinase II; CREB, cyclic AMP-responsive element binding protein; Cyt, cytosolic; EMSA, electrophoretic mobility shift assay; FGF, fibroblast growth factor; GluR2/3, glutamate receptor 2/3; GSK3, glycogen synthase kinase 3; NF-κB, nuclear factor-κB; NMDAR2B, NMDA receptor 2B; nsMit, nonsynaptic mitochondria; Nuc, nuclear; pCREB, Ser133 phosphorylated form of CREB; PKA, protein kinase A; PP, protein phosphatase; Psd, postsynaptic densities; sMit, synaptic mitochondria; Spm, synaptic plasma membranes; Syn, synaptosomes.
- Issue published online: 18 JAN 2002
- Article first published online: 18 JAN 2002
- Cyclic AMP-responsive element binding protein;
- Brain mitochondria
Abstract: Cyclic AMP-responsive element binding protein (CREB) is critically involved in many important brain functions, including the formation of long-term memory. CREB is the best characterized member of a family of transcription factors (CREB/ATF family) recognized to be important nuclear targets for intracellular signal transduction systems. Here we show, by using different approaches, that CREB is unexpectedly localized to mitochondria of the rat brain. Controlled subcellular fractionation of hippocampus and cerebral cortex showed that both synaptic and nonsynaptic mitochondria exhibited immunoreactivity to the phosphorylated form of CREB (pCREB). Moreover, CREB extracted from synaptic mitochondria is able to be phosphorylated by the catalytic subunit of protein kinase A and dephosphorylated by protein phosphatase 1 or 2B. DNA mobility shift assays showed the presence of binding activity to the calcium—cyclic AMP-responsive element in mitochondrial extracts from hippocampus; this binding complex was specifically supershifted by an anti-CREB antibody. Immunoelectron microscopic analysis of hippocampal subcellular fractions revealed that pCREB immunoreactivity is localized in close association with the inner mitochondrial membrane. These results, together with recent findings describing the presence and phosphorylation of CREB in developing dendrites, suggest that CREB may participate in different mechanisms involved in the communication between extracellular signals and the expression of genes.