Akio Wanaka

Bio: Akio Wanaka is an academic researcher from Nara Medical University. The author has contributed to research in topics: Gene expression & Embryonic stem cell. The author has an hindex of 47, co-authored 164 publications receiving 7024 citations. Previous affiliations of Akio Wanaka include Washington University in St. Louis & Fukushima Medical University.

Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation.

Abstract: Eukaryotic cells have signalling pathways from the endoplasmic reticulum (ER) to cytosol and nuclei, to avoid excess accumulation of unfolded proteins in the ER. We previously identified a new type of ER stress transducer, OASIS, a bZIP (basic leucine zipper) transcription factor, which is a member of the CREB/ATF family and has a transmembrane domain. OASIS is processed by regulated intramembrane proteolysis (RIP) in response to ER stress, and is highly expressed in osteoblasts. OASIS(-/-) mice exhibited severe osteopenia, involving a decrease in type I collagen in the bone matrix and a decline in the activity of osteoblasts, which showed abnormally expanded rough ER, containing of a large amount of bone matrix proteins. Here we identify the gene for type 1 collagen, Col1a1, as a target of OASIS, and demonstrate that OASIS activates the transcription of Col1a1 through an unfolded protein response element (UPRE)-like sequence in the osteoblast-specific Col1a1 promoter region. Moreover, expression of OASIS in osteoblasts is induced by BMP2 (bone morphogenetic protein 2), the signalling of which is required for bone formation. Additionally, RIP of OASIS is accelerated by BMP2 signalling, which causes mild ER stress. Our studies show that OASIS is critical for bone formation through the transcription of Col1a1 and the secretion of bone matrix proteins, and they reveal a new mechanism by which ER stress-induced signalling mediates bone formation.

OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes

Abstract: Endoplasmic reticulum (ER) stress transducers IRE1, PERK and ATF6 are well known to transduce signals from the ER to the cytoplasm and nucleus when unfolded proteins are accumulated in the ER. Here, we identified OASIS as a novel ER stress transducer. OASIS is a basic leucine zipper (bZIP) transcription factor of the CREB/ATF family with a transmembrane domain that allows it to associate with the ER. The molecule is cleaved at the membrane in response to ER stress, and its cleaved amino-terminal cytoplasmic domain, which contains the bZIP domain, translocates into the nucleus where it activates the transcription of target genes that are mediated by ER stress-responsive and cyclic AMP-responsive elements. Intriguingly, OASIS was induced at the transcriptional level during ER stress in astrocytes of the central nervous system, but not in other cell types examined. Furthermore, overexpression of OASIS resulted in induction of BiP and suppression of ER-stress-induced cell death, whereas knockdown partially reduced BiP levels and led to ER stress in susceptible astrocytes. Our results reveal pivotal roles for OASIS in modulating the unfolded protein response in astrocytes, and the possibility that cell type-specific UPR signalling also exists in other cells.

Expression of FGF receptor gene in rat development

Abstract: We examined the expression of FGF-receptor (FGF-R) mRNA during rat development with in situ hybridization histochemistry. Embryonic tissues (E9, E12, E14, E17) and postnatal neural tissues (P1, P7, P14, adult) were examined. We detected significant levels of FGF-R mRNA in various tissues at different developmental stages. As postulated by previous studies using other methods, FGF-R gene expression was observed primarily in mesoderm- and neuroectoderm-derived tissues. In the nervous system, the pattern of gene expression was developmentally regulated; in embryos, FGF-R mRNA was mainly detected in the ependymal layer of the central nervous system (CNS). Postnatally, FGF-R transcripts were observed in specific neuronal populations, such as hippocampal neurons. FGF-R mRNA was also found in sensory systems such as trigeminal and dorsal root ganglia in late stage embryos; however, FGF-R mRNA decreased in the postnatal period. FGF-R mRNA expression was modulated in the developing retina: FGF-R messages were observed in the pigment epithelium and neuroblast layer at embryonic stages; in the postnatal period, they were found in the ganglion cell and inner granular layer. In non-neuronal embryonic tissues, a wide variety of organs expressed FGF-R message. Particularly, the prevertebral column, bone, kidney and skin showed high levels of expression. These observations reinforce the idea that FGF exerts effects on the development of various tissues.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

The Bcl2 family: regulators of the cellular life-or-death switch.

Abstract: Tissue homeostasis is regulated by apoptosis, the cell-suicide programme that is executed by proteases called caspases. The Bcl2 family of intracellular proteins is the central regulator of caspase activation, and its opposing factions of anti- and pro-apoptotic members arbitrate the life-or-death decision. Apoptosis is often impaired in cancer and can limit conventional therapy. A better understanding of how the Bcl2 family controls caspase activation should result in new, more effective therapeutic approaches.

Ischemic Cell Death in Brain Neurons

Abstract: This review is directed at understanding how neuronal death occurs in two distinct insults, global ischemia and focal ischemia. These are the two principal rodent models for human disease. Cell dea...

Regeneration beyond the glial scar

Abstract: After injury to the adult central nervous system (CNS), injured axons cannot regenerate past the lesion. In this review, we present evidence that this is due to the formation of a glial scar. Chondroitin and keratan sulphate proteoglycans are among the main inhibitory extracellular matrix molecules that are produced by reactive astrocytes in the glial scar, and they are believed to play a crucial part in regeneration failure. We will focus on this role, as well as considering the behaviour of regenerating neurons in the environment of CNS injury.