The two-domain architecture of LAMP2A within the lysosomal lumen regulates its interaction with HSPA8/Hsc70

Chaperone-mediated autophagy (CMA) is a unique proteolytic pathway, in which cytoplasmic proteins recognized by HSPA8/Hsc70 (heat shock protein 8) are transported into lysosomes for degradation. LAMP2A (lysosomal-associated membrane protein 2A) recruits the substrate/chaperone complex to the lysosome membrane. The structure of LAMP2A comprises a large lumenal domain composed of two homologous subdomains (N-domain and C-domain, both with the β-prism fold), a transmembrane domain, and a short cytoplasmic tail. Although the homophilic interaction between LAMP2A molecules and the interaction between HSPA8 and LAMP2A have been suggested, whether the interactions are direct or mediated by other molecules has remained to be elucidated. We investigated the interactions by using expanded genetic code technologies that generate photo-crosslinking and/or steric hindrance at specified interfaces in mammalian cells. The results suggested that LAMP2A molecules assemble by facing each other with one side of the β-prism in their C-domains. We also detected the photo-crosslinking between the cytoplasmic tail of LAMP2A and HSPA8, revealing this direct interaction. We found that the truncation of the N-domain reduced the amount of HSPA8 that coimmunoprecipitates with LAMP2A. Our present results suggest that the two-domain architecture of the lumenal domains of LAMP2A underlies the interaction with HSPA8 at the cytoplasmic surface of the lysosome

新潟県中越沖地震直後の海水の性質(資料)

金沢大学理工研究域地球社会基盤学

Breakdown characteristics in DC spark experiments of copper focusing on purity and hardness

The breakdown characteristics related to the differences in purity and hardness were investigated for several types of copper using a DC spark test system. Three types of oxygen-free copper (OFC) materials, usual class 1 OFC 7-nine large-grain copper and 6-nine hot-isotropic-pressed (HIP) copper with/without diamond finish, were tested with the DC spark test system. The measurements of the beta, breakdown fields, and breakdown probability are presented and discussed in this paper

YM750, an ACAT Inhibitor, Acts on Adrenocortical Cells to Inhibit Aldosterone Secretion Due to Depolarization

Primary aldosteronism (PA) is considered the most common form of secondary hypertension, which is associated with excessive aldosterone secretion in the adrenal cortex. The cause of excessive aldosterone secretion is the induction of aldosterone synthase gene (CYP11B2) expression by depolarization of adrenocortical cells. In this study, we found that YM750, an Acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, acts on adrenocortical cells to suppress CYP11B2 gene expression and aldosterone secretion. YM750 inhibited the induction of CYP11B2 gene expression by KCl stimulation, but not by angiotensin II and forskolin stimulation. Interestingly, YM750 did not inhibit KCl-stimulated depolarization via an increase in intracellular calcium ion concentration. Moreover, ACAT1 expression was relatively abundant in the zona glomerulosa (ZG) including these CYP11B2-positive cells. Thus, YM750 suppresses CYP11B2 gene expression by suppressing intracellular signaling activated by depolarization. In addition, ACAT1 was suggested to play an important role in steroidogenesis in the ZG. YM750 suppresses CYP11B2 gene expression and aldosterone secretion in the adrenal cortex, suggesting that it may be a potential therapeutic agent for PA