The analysis of the nucleus-endoplasmic reticulum communication zone involved in the DNA damage response.

Research abstract

The nucleus is covered with the nuclear envelope composed of inner (INM) and outer nuclear membranes (ONM). INM and ONM are connected via nuclear pore complex (NPC), and ONM is continuous with the membrane of endoplasmic reticulum (ER). The proteins localized in INM are originally synthesized in ER, followed by transport of the proteins into INM via ONM and NPC, indicating that nuclear envelope and ER membrane structurally and functionally communicate each other. However, precise mechanisms of molecular trafficking of INM proteins have not been elucidated. Further, it also remains unclear how the ER responds to the intranuclear events including DNA damages and regulates the nuclear functions.
We recently found that OASIS, one of the ER-resident transmembrane proteins, focally accumulates on the membrane of nuclear blebs or micronuclei that are formed during DNA damages. OASIS-deficient cells are more sensitive to DNA damage than wild-type cells. The dynamic movement of OASIS at focal region of nuclear membrane may be important for DNA damage response. We define the areas where OASIS focally accumulates as “nucleus-ER communication zone” in this project. Now, we are investigating 1) mechanisms of translocation of OASIS from ER into nuclear membrane, and 2) the roles of OASIS in the DNA damage response. We also try to identify the components, spatiotemporal regulation and physiological roles of the nucleus-ER communication zone.

Original papers

1. Ohtake Y, Matsuhisa K, Kaneko M, Kanemoto S, Asada R, Imaizumi K, and Saito A. (2018) Axonal Activation of the Unfolded Protein Response Promotes Axonal Regeneration Following Peripheral Nerve Injury. Neuroscience, 375:34-48.
2. Wu Y, Guo XP, Kanemoto S, Maeoka Y, Saito A, Asada R, Matsuhisa K, Ohtake Y, Imaizumi K, and Kaneko M. (2018) Sec16A, a key protein in COPII vesicle formation, regulates the stability and localization of the novel ubiquitin ligase RNF183. Plos One, 13: e0190407.
3. Saito A, Cai L, Matsuhisa K, Ohtake Y, Kaneko M, Kanemoto S, Asada R, Imaizumi K. (2017) Neuronal activity-dependent local activation of dendritic unfolded protein response promotes expression of brain-derived neurotrophic factor in cell soma, Journal of Neurochemistry, 144:35-49.