Physiological functions of endoplasmic reticulum stress transducer OASIS in central nervous system

Eukaryotic cells can adapt to endoplasmic reticulum (ER) dysfunction by producing diverse signals from the ER to the cytosol or nucleus. These signaling pathways are collectively known as the unfolded protein response (UPR). The canonical branches of the UPR are mediated by three ER membrane-bound proteins: double-stranded RNA-dependent protein kinase (PKR)-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE1) and activating transcription factor 6 (ATF6). These ER stress transducers basically play important roles in cell survival after ER stress. Recently, novel types of ER stress transducers that share a region of high sequence similarity with ATF6 have been identified. They have a transmembrane domain, which allows them to associate with the ER, and possess a transcription-activation domain and a basic leucine zipper (bZIP) domain. These membrane-bound bZIP transcription factors include OASIS, BBF2H7 CREBH, CREB4 and Luman, and are collectively referred to as OASIS family members. Despite their structural similarities with ATF6, differences in activating stimuli and tissue distribution indicate specialized functions of each member on regulating UPR signaling in specific organs and tissues. One of them, OASIS, is expressed preferentially in astrocytes in the central nervous system (CNS). OASIS temporally regulates the differentiation from neural precursor cells into astrocytes to promote the expression of Glial Cell Missing 1 through dynamic interactions among OASIS family members followed by accelerating demethylation of the Gfap promoter. This review is a summary of our current understanding of the physiological functions of OASIS in the CNS.