A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes

The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells. It comprises one catalytic 20S proteasome and two axially positioned 19S regulatory complexes. The 20S proteasome is composed of 28 subunits arranged in a cylindrical particle as four heteroheptameric rings, alpha1-7beta1-7beta1-7alpha1-7 (refs 4, 5), but the mechanism responsible for the assembly of such a complex structure remains elusive. Here we report two chaperones, designated proteasome assembling chaperone-1 (PAC1) and PAC2, that are involved in the maturation of mammalian 20S proteasomes. PAC1 and PAC2 associate as heterodimers with proteasome precursors and are degraded after formation of the 20S proteasome is completed. Overexpression of PAC1 or PAC2 accelerates the formation of precursor proteasomes, whereas knockdown by short interfering RNA impairs it, resulting in poor maturation of 20S proteasomes. Furthermore, the PAC complex provides a scaffold for alpha-ring formation and keeps the alpha-rings competent for the subsequent formation of half-proteasomes. Thus, our results identify a mechanism for the correct assembly of 20S proteasomes.     

Deciduoma formation in rats with cornified vagina

Summary In female rats given a single injection of 1.25 mg 5-dihydrotestosterone during neonatal life, reactivity of the vaginal mucosa to hormones was permanently altered, so that the rats, when adult, could show vaginal cornification under the hormonic conditions supportive of development of deciduomata in the uterus.We wish to thank Prof.T. Kimoto of Kawasaki Medical College for valuable advice and information.     

Partial purification of an endogenous elicitor from suspension-cultured cells of red bean,Vigna angularis

Brief irradiation with a germicidal UV lamp of cells of red bean,Vigna angularis, cultured in suspension in a quartz flask caused the release into the culture medium of an endogenous substance with elicitor activity, as well as the accumulation of isoflavone glucoside stress metabolites in the cells. The active compound was fractionated using phenylalanine ammonia lyase (PAL)-inducing activity in fresh cells as a marker. The elicitor active principle appears to be a low molecular weight (<2000 MW) water-soluble acidic oligosaccharide.     

IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis

Insulin-like growth-factor-binding proteins (IGFBPs) bind to and modulate the actions of insulin-like growth factors (IGFs). Although some of the actions of IGFBPs have been reported to be independent of IGFs, the precise mechanisms of IGF-independent actions of IGFBPs are largely unknown. Here we report a previously unknown function for IGFBP-4 as a cardiogenic growth factor. IGFBP-4 enhanced cardiomyocyte differentiation in vitro, and knockdown of Igfbp4 attenuated cardiomyogenesis both in vitro and in vivo. The cardiogenic effect of IGFBP-4 was independent of its IGF-binding activity but was mediated by the inhibitory effect on canonical Wnt signalling. IGFBP-4 physically interacted with a Wnt receptor, Frizzled 8 (Frz8), and a Wnt co-receptor, low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited the binding of Wnt3A to Frz8 and LRP6. Although IGF-independent, the cardiogenic effect of IGFBP-4 was attenuated by IGFs through IGFBP-4 sequestration. IGFBP-4 is therefore an inhibitor of the canonical Wnt signalling required for cardiogenesis and provides a molecular link between IGF signalling and Wnt signalling.     

Revision of the sesarmid crab genera Labuanium Serène and Soh, 1970, Scandarma Schubart,Liu and Cuesta, 2003 and Namlacium Serène and Soh, 1970 (Crustacea: Decapoda: Brachyura: Sesarmidae), with descriptions of four new genera and two new species

ABSTRACT

The systematics of the arboreal sesarmid crab genera Labuanium Serène and Soh, 1970 and Scandarma Schubart, Liu and Cuesta, 2003 is revised. Also included is the poorly known genus Namlacium Serène and Soh, 1970, which is morphologically similar to Labuanium and may also be arboreal in habit. The present study restricts Labuanium to its type species, L. politum (De Man, 1887), and congeners are transferred to Scandarma, Geosesarma De Man, 1892, and three new genera established herein: Circulium gen. nov., Shinobium gen. nov. and Mindanium gen. nov. Two new species of Scandarma are described from Papua New Guinea and Madagascar. Sesarma jacquinoti Ortmann, 1894, previously regarded as a synonym of Scandarma gracilipes (H. Milne Edwards, 1853) (comb. nov.), is here shown to be a junior synonym of Sesarmops angustifrons (A. Milne-Edwards, 1869). Labuanium schuetteii (Hess, 1865) is regarded as conspecific with Scandarma gracilipes (H. Milne Edwards, 1853) (comb. nov.) and the lectotype of the latter species (here designated) is also selected as the neotype of the former, making the two names objective synonyms. Material which had been identified as ‘Labuanium finni Alcock, 1900’ by Pretzmann (1984) from the South Andaman Islands is actually the poorly known Geosesarma thelxinoe (De Man, 1908), which is here referred to a new genus, Andamanium gen. nov. Sesarma finni Alcock, 1900 s.s. is herein assigned to Scandarma. Namlacium crepidatum (Calman, 1925), the only species in the genus, is redescribed and figured and compared with Labuanium and Scandarma. Keys to species of Circulium and Scandarma are provided.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:414B8DAA-584F-4070-A355-83B583D0D017     

A SNP in the ABCC11 gene is the determinant of human earwax type

Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. Here we show that a SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of Asian ancestry. A functional assay demonstrated that cells with allele A show a lower excretory activity for cGMP than those with allele G. The allele A frequency shows a north-south and east-west downward geographical gradient; worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype is retained among various ethnic populations. These suggest that the allele A arose in northeast Asia and thereafter spread through the world. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait.     

Distinct roles of the FliI ATPase and proton motive force in bacterial flagellar protein export

Translocation of many soluble proteins across cell membranes occurs in an ATPase-driven manner. For construction of the bacterial flagellum responsible for motility, most of the components are exported by the flagellar protein export apparatus. The FliI ATPase is required for this export, and its ATPase activity is regulated by FliH; however, it is unclear how the chemical energy derived from ATP hydrolysis is used for the export process. Here we report that flagellar proteins of Salmonella enterica serovar Typhimurium are exported even in the absence of FliI. A fliH fliI double null mutant was weakly motile. Certain mutations in FlhA or FlhB, which form the core of the export gate, substantially improved protein export and motility of the double null mutant. Furthermore, proton motive force was essential for the export process. These results suggest that the FliH-FliI complex facilitates only the initial entry of export substrates into the gate, with the energy of ATP hydrolysis being used to disassemble and release the FliH-FliI complex from the protein about to be exported. The rest of the successive unfolding/translocation process of the substrates is driven by proton motive force.     

Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population

Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.