Aoki N

References (3)

Title : Autism-associated variants of neuroligin 4X impair synaptogenic activity by various molecular mechanisms - Yumoto_2020_Mol.Autism_11_68
Author(s) : Yumoto T , Kimura M , Nagatomo R , Sato T , Utsunomiya S , Aoki N , Kitaura M , Takahashi K , Takemoto H , Watanabe H , Okano H , Yoshida F , Nao Y , Tomita T
Ref : Mol Autism , 11 :68 , 2020
Abstract : BACKGROUND: Several genetic alterations, including point mutations and copy number variations in NLGN genes, have been associated with psychiatric disorders, such as autism spectrum disorder (ASD) and X-linked mental retardation (XLMR). NLGN genes encode neuroligin (NL) proteins, which are adhesion molecules that are important for proper synaptic formation and maturation. Previously, we and others found that the expression level of murine NL1 is regulated by proteolytic processing in a synaptic activity-dependent manner. METHODS: In this study, we analyzed the effects of missense variants associated with ASD and XLMR on the metabolism and function of NL4X, a protein which is encoded by the NLGN4X gene and is expressed only in humans, using cultured cells, primary neurons from rodents, and human induced pluripotent stem cell-derived neurons. RESULTS: NL4X was found to undergo proteolytic processing in human neuronal cells. Almost all NL4X variants caused a substantial decrease in the levels of mature NL4X and its synaptogenic activity in a heterologous culture system. Intriguingly, the L593F variant of NL4X accelerated the proteolysis of mature NL4X proteins located on the cell surface. In contrast, other variants decreased the cell-surface trafficking of NL4X. Notably, protease inhibitors as well as chemical chaperones rescued the expression of mature NL4X. LIMITATIONS: Our study did not reveal whether these dysfunctional phenotypes occurred in individuals carrying NLGN4X variant. Moreover, though these pathological mechanisms could be exploited as potential drug targets for ASD, it remains unclear whether these compounds would have beneficial effects on ASD model animals and patients. CONCLUSIONS: These data suggest that reduced amounts of the functional NL4X protein on the cell surface is a common mechanism by which point mutants of the NL4X protein cause psychiatric disorders, although different molecular mechanisms are thought to be involved. Furthermore, these results highlight that the precision medicine approach based on genetic and cell biological analyses is important for the development of therapeutics for psychiatric disorders.
ESTHER : Yumoto_2020_Mol.Autism_11_68
PubMedSearch : Yumoto_2020_Mol.Autism_11_68
PubMedID: 32873342

Title : Whole genome sequence of Desulfovibrio magneticus strain RS-1 revealed common gene clusters in magnetotactic bacteria - Nakazawa_2009_Genome.Res_19_1801
Author(s) : Nakazawa H , Arakaki A , Narita-Yamada S , Yashiro I , Jinno K , Aoki N , Tsuruyama A , Okamura Y , Tanikawa S , Fujita N , Takeyama H , Matsunaga T
Ref : Genome Res , 19 :1801 , 2009
Abstract : Magnetotactic bacteria are ubiquitous microorganisms that synthesize intracellular magnetite particles (magnetosomes) by accumulating Fe ions from aquatic environments. Recent molecular studies, including comprehensive proteomic, transcriptomic, and genomic analyses, have considerably improved our hypotheses of the magnetosome-formation mechanism. However, most of these studies have been conducted using pure-cultured bacterial strains of alpha-proteobacteria. Here, we report the whole-genome sequence of Desulfovibrio magneticus strain RS-1, the only isolate of magnetotactic microorganisms classified under delta-proteobacteria. Comparative genomics of the RS-1 and four alpha-proteobacterial strains revealed the presence of three separate gene regions (nuo and mamAB-like gene clusters, and gene region of a cryptic plasmid) conserved in all magnetotactic bacteria. The nuo gene cluster, encoding NADH dehydrogenase (complex I), was also common to the genomes of three iron-reducing bacteria exhibiting uncontrolled extracellular and/or intracellular magnetite synthesis. A cryptic plasmid, pDMC1, encodes three homologous genes that exhibit high similarities with those of other magnetotactic bacterial strains. In addition, the mamAB-like gene cluster, encoding the key components for magnetosome formation such as iron transport and magnetosome alignment, was conserved only in the genomes of magnetotactic bacteria as a similar genomic island-like structure. Our findings suggest the presence of core genetic components for magnetosome biosynthesis; these genes may have been acquired into the magnetotactic bacterial genomes by multiple gene-transfer events during proteobacterial evolution.
ESTHER : Nakazawa_2009_Genome.Res_19_1801
PubMedSearch : Nakazawa_2009_Genome.Res_19_1801
PubMedID: 19675025
Gene_locus related to this paper: desmr-c4xjz8 , desmr-c4xl23 , desmr-c4xq70 , desmr-c4xqs3 , desmr-c4xr42 , desmr-c4xr97 , desmr-metxa

Title : The DNA sequence of human chromosome 22 - Dunham_1999_Nature_402_489
Author(s) : Dunham I , Hunt AR , Collins JE , Bruskiewich R , Beare DM , Clamp M , Smink LJ , Ainscough R , Almeida JP , Babbage AK , Bagguley C , Bailey J , Barlow KF , Bates KN , Beasley OP , Bird CP , Blakey SE , Bridgeman AM , Buck D , Burgess J , Burrill WD , Burton J , Carder C , Carter NP , Chen Y , Clark G , Clegg SM , Cobley VE , Cole CG , Collier RE , Connor R , Conroy D , Corby NR , Coville GJ , Cox AV , Davis J , Dawson E , Dhami PD , Dockree C , Dodsworth SJ , Durbin RM , Ellington AG , Evans KL , Fey JM , Fleming K , French L , Garner AA , Gilbert JGR , Goward ME , Grafham DV , Griffiths MND , Hall C , Hall RE , Hall-Tamlyn G , Heathcott RW , Ho S , Holmes S , Hunt SE , Jones MC , Kershaw J , Kimberley AM , King A , Laird GK , Langford CF , Leversha MA , Lloyd C , Lloyd DM , Martyn ID , Mashreghi-Mohammadi M , Matthews LH , Mccann OT , Mcclay J , Mclaren S , McMurray AA , Milne SA , Mortimore BJ , Odell CN , Pavitt R , Pearce AV , Pearson D , Phillimore BJCT , Phillips SH , Plumb RW , Ramsay H , Ramsey Y , Rogers L , Ross MT , Scott CE , Sehra HK , Skuce CD , Smalley S , Smith ML , Soderlund C , Spragon L , Steward CA , Sulston JE , Swann RM , Vaudin M , Wall M , Wallis JM , Whiteley MN , Willey DL , Williams L , Williams SA , Williamson H , Wilmer TE , Wilming L , Wright CL , Hubbard T , Bentley DR , Beck S , Rogers J , Shimizu N , Minoshima S , Kawasaki K , Sasaki T , Asakawa S , Kudoh J , Shintani A , Shibuya K , Yoshizaki Y , Aoki N , Mitsuyama S , Roe BA , Chen F , Chu L , Crabtree J , Deschamps S , Do A , Do T , Dorman A , Fang F , Fu Y , Hu P , Hua A , Kenton S , Lai H , Lao HI , Lewis J , Lewis S , Lin S-P , Loh P , Malaj E , Nguyen T , Pan H , Phan S , Qi S , Qian Y , Ray L , Ren Q , Shaull S , Sloan D , Song L , Wang Q , Wang Y , Wang Z , White J , Willingham D , Wu H , Yao Z , Zhan M , Zhang G , Chissoe S , Murray J , Miller N , Minx P , Fulton R , Johnson D , Bemis G , Bentley D , Bradshaw H , Bourne S , Cordes M , Du Z , Fulton L , Goela D , Graves T , Hawkins J , Hinds K , Kemp K , Latreille P , Layman D , Ozersky P , Rohlfing T , Scheet P , Walker C , Wamsley A , Wohldmann P , Pepin K , Nelson J , Korf I , Bedell JA , Hillier L , Mardis E , Waterston R , Wilson R , Emanuel BS , Shaikh T , Kurahashi H , Saitta S , Budarf ML , McDermid HE , Johnson A , Wong ACC , Morrow BE , Edelmann L , Kim UJ , Shizuya H , Simon MI , Dumanski JP , Peyrard M , Kedra D , Seroussi E , Fransson I , Tapia I , Bruder CE , O'Brien KP
Ref : Nature , 402 :489 , 1999
Abstract : Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.
ESTHER : Dunham_1999_Nature_402_489
PubMedSearch : Dunham_1999_Nature_402_489
PubMedID: 10591208
Gene_locus related to this paper: human-CES5A , human-SERHL2