CPEB4 is a cell survival protein retained in the nucleus upon ischemia or endoplasmic reticulum calcium depletion
Department of Cell Biology; Program in Molecular Medicine
Medical Subject Headings
Amino Acid Sequence; Animals; Brain Ischemia; Calcium; Cell Nucleus; Cells, Cultured; Endoplasmic Reticulum; Humans; Molecular Sequence Data; N-Methylaspartate; Neurons; Protein Isoforms; RNA-Binding Proteins; Rats; Receptors, Ionotropic Glutamate; Recombinant Fusion Proteins; Sodium Channel Blockers; Tetrodotoxin
The RNA binding protein CPEB (cytoplasmic polyadenylation element binding) regulates cytoplasmic polyadenylation and translation in germ cells and the brain. In neurons, CPEB is detected at postsynaptic sites, as well as in the cell body. The related CPEB3 protein also regulates translation in neurons, albeit probably not through polyadenylation; it, as well as CPEB4, is present in dendrites and the cell body. Here, we show that treatment of neurons with ionotropic glutamate receptor agonists causes CPEB4 to accumulate in the nucleus. All CPEB proteins are nucleus-cytoplasm shuttling proteins that are retained in the nucleus in response to calcium-mediated signaling and alpha-calcium/calmodulin-dependent kinase protein II (CaMKII) activity. CPEB2, -3, and -4 have conserved nuclear export signals that are not present in CPEB. CPEB4 is necessary for cell survival and becomes nuclear in response to focal ischemia in vivo and when cultured neurons are deprived of oxygen and glucose. Further analysis indicates that nuclear accumulation of CPEB4 is controlled by the depletion of calcium from the ER, specifically, through the inositol-1,4,5-triphosphate (IP3) receptor, indicating a communication between these organelles in redistributing proteins between subcellular compartments.
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Citation: Mol Cell Biol. 2010 Dec;30(24):5658-71. Epub 2010 Oct 11. Link to article on publisher's site
Kan, Ming-Chung; Oruganty-Das, Aparna; Cooper-Morgan, Amalene; Jin, Guang; Swanger, Sharon A.; Bassell, Gary J.; Florman, Harvey M.; van Leyen, Klaus; and Richter, Joel D., "CPEB4 is a cell survival protein retained in the nucleus upon ischemia or endoplasmic reticulum calcium depletion" (2010). Florman Lab. 1.