Issue Cover (January 2018)

Front cover: Unfolded protein response (UPR) has roles not only in resolving the accumulation of unfolded proteins owing to endoplasmic reticulum (ER) stress, but also in regulation of cellular physiological functions. Here, we demonstrated that synaptic activity‐ and brain‐derived neurotrophic factor (BDNF)‐dependent local activation of UPR signaling could be associated with dendritic functions through retrograde signal propagation by using murine neuroblastoma cell lines and primary cultured mouse hippocampal neurons. One of the UPR branches, inositol‐requiring kinase 1 (IRE1) pathway, was activated in response to excitatory synaptic activation. Dendritic IRE1 was phosphorylated at post synaptic sites after excitatory synaptic activation, followed by accumulation of x‐box binding protein 1 (XBP1) into the nucleus. XBP1 promoted transcriptional activation of Bdnf . BDNF in turn drove its own expression via protein kinase A (PKA)‐dependent activation of dendritic IRE1‐XBP1 signaling. Synaptic activity‐ and BDNF‐dependent distinct activation of dendritic IRE1‐XBP1 cascade may comprehensively regulate dendritic extension through the expression of BDNF. The image shows the immunofluorescence staining analysis of green fluorescence protein (GFP) (green), spliced form of XBP1 (XBP1s) (red) and microtubule‐associated protein 2 (MAP2) (blue) in primary cultured mouse hippocampal neurons maintained for 10 days. The cells were infected with lentiviruses expressing scrambled shRNA with GFP for 5 days and treated with 7.5 μM glutamate for 12 h. XBP1s accumulated in the nucleus in response to glutamate stimulation.Read the full article ‘Neuronal activity‐dependent local activation of dendritic unfolded protein response promotes expression of brain‐derived neurotrophic factor in cell soma’ by A. Saito, L. Cai, K. Matsuhisa, Y. Ohtake, M. Kaneko, S. Kanemoto, R. Asada and K. Imaizumi ( J. Neurochem . 2018, vol. 144(1), pp. 35–49) on doi: 10.1111/jnc.14221