- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Proteoglycans and glycosaminoglycans research
- Glycosylation and Glycoproteins Research
- Hippo pathway signaling and YAP/TAZ
- Developmental Biology and Gene Regulation
- Cellular Mechanics and Interactions
- Endoplasmic Reticulum Stress and Disease
- Protease and Inhibitor Mechanisms
- Galectins and Cancer Biology
- Studies on Chitinases and Chitosanases
- Reproductive Biology and Fertility
- Trace Elements in Health
- Enzyme Structure and Function
- Chromosomal and Genetic Variations
- Allergic Rhinitis and Sensitization
- RNA Research and Splicing
- Lysosomal Storage Disorders Research
- Evolution and Genetic Dynamics
- Biochemical and Molecular Research
- Proteins in Food Systems
- thermodynamics and calorimetric analyses
- Digestive system and related health
- Lipid metabolism and biosynthesis
- Polysaccharides and Plant Cell Walls
Tokyo Women's Medical University
2014-2023
Japan Science and Technology Agency
2007-2020
Kyushu University
2003-2018
University of California, San Diego
2014
University of Minnesota
2010-2013
Twin Cities Orthopedics
2012
Tokyo Institute of Technology
2009
Kawaguchi Junior College
2003-2006
Kyoto first Red Cross hospital
1992-1995
Kyoto Prefectural University of Medicine
1986
Balancer chromosomes are critical tools for genetic research. In C. elegans, reciprocal translocations that lead to aneuploidy have been widely used maintain lethal and sterile mutations in stable stocks. Here, we generated a set of aneuploidy-free structurally defined crossover suppressors contain two overlapping inversions using the CRISPR/Cas9 system. The toolkit includes 13 covers approximately 63% all elegans coding genes. Together with classical intrachromosomal suppressors, system now...
We previously proposed a model that DALLY, Drosophila glypican, acts as trans co-receptor to regulate BMP signaling in the germ line stem cell niche. To investigate molecular mechanisms of contact-dependent signaling, we developed novel vitro assay systems monitor using S2 cells. Using immunoblot-based well single-cell systems, present evidence glypicans indeed enhance manner vitro. Our analysis showed heparan sulfate modification is required for activity DALLY. Two BMP-like molecules,...
In Drosophila, ligands of the Unpaired (Upd) family activate Janus kinase/signal transducers and activators transcription (JAK/STAT) pathway. The JAK/STAT pathway controls many developmental events, including multiple functions in ovary. These include an early role germarium for specification stalk cells a later vitellarium to pattern follicular epithelium surrounding each cyst. this latter role, graded activation specifies three distinct anterior cell fates, suggesting that Upd is morphogen...
Galectins are a family of β-galactoside-binding proteins that widely found among animal species and regulate diverse biological phenomena. To study the function glycolipid-binding galectins, we purified recombinant Caenorhabditis elegans galectins (LEC-1–11) studied their binding to C. glycolipids. We LEC-8 binds glycolipids in through carbohydrate recognition. It has been reported Cry5B-producing Bacillus thuringiensis strains can infect Cry5B receptor molecules bound glycolipid-coated...
Ceramide glucosyltransferase (Ugcg) [uridine diphosphate (UDP)-glucose:N-acylsphingosine d-glucosyltransferase or UDP-glucose ceramide (GlcT): EC 2.4.1.80] catalyzes formation of glucosylceramide (GlcCer) from and UDP-glucose. There is only one Ugcg gene in the mouse genome, which essential embryogenesis brain development. The nematode Caenorhabditis elegans has three genes (cgt-1, cgt-2 cgt-3), double RNAi cgt-1 cgt-3 results lethality at L1 larval stage. In this study, we isolated knockout...
Glycosylphosphatidylinositol (GPI)-anchor attachment is one of the most common posttranslational protein modifications. Using nematode Caenorhabditis elegans, we determined that GPI-anchored proteins are present in germline cells and distal tip cells, which essential for maintenance stem cell niche. We identified 24 C. elegans genes involved GPI-anchor synthesis. Inhibition various steps synthesis by RNA interference or gene knockout resulted abnormal development oocytes early embryos, both...
The proteins encoded by all of the five cloned human EXT family genes (EXT1, EXT2, EXTL1, EXTL2, and EXTL3), members hereditary multiple exostoses gene tumor suppressors, are glycosyltransferases required for biosynthesis heparan sulfate. In Caenorhabditis elegans genome, only two genes, rib-1 rib-2, homologous to mammalian have been identified. Although rib-2 encodes an N-acetylglucosaminyltransferase involved in initiating elongation sulfate, involvement protein sulfate remains unclear....
Heparan sulfate proteoglycans regulate various physiological and developmental processes through interactions with a number of protein ligands. (HS)-ligand binding depends on the amount patterns groups HS, which are controlled by HS sulfotransferases in Golgi apparatus as well extracellular 6-O-endosulfatases called "Sulfs." Sulfs family secreted molecules that specifically remove 6-O-sulfate within highly sulfated regions HS. Vertebrate promote Wnt signaling, whereas only Drosophila...
During the biosynthesis of heparan sulfate (HS), glucuronyl C5-epimerase (Hsepi) catalyzes C5-epimerization glucuronic acid (GlcA), converting it to iduronic (IdoA). Because HS 2-O-sulfotransferase (Hs2st) shows a strong substrate preference for IdoA over GlcA, is required normal sulfation. However, physiological significance remains elusive. To understand role Hsepi in development, we isolated Drosophila mutants. Homozygous mutants are viable and fertile with only minor morphological...
Wnt signals orient mitotic spindles in development, but it remains unclear how signaling is spatially controlled to achieve precise spindle orientation. Here, we show that C. elegans syndecan (SDN-1) required for orientation of a response cue. We find SDN-1 the predominant heparan sulfate (HS) proteoglycan early embryo, and loss HS biosynthesis or core protein results misorientation ABar blastomere. The EMS both reorient signals, only reorientation dependent on new cell contact SDN-1....
Although the solute carrier 35B1 (SLC35B1) is evolutionarily conserved, its functions in metazoans remain unknown. To elucidate function, we examined developmental roles of an SLC35B1 family gene (HUT-1: homolog UDP-Gal transporter) Caenorhabditis elegans. We isolated a deletion mutant and characterized phenotypes hut-1 RNAi-treated worms. GFP-HUT-1 reporter analysis was performed to examine expression patterns. also tested whether several nucleotide sugar transporters can compensate for...
Synthesis of extracellular sulfated molecules requires active 3′-phosphoadenosine 5′-phosphosulfate (PAPS). For sulfation to occur, PAPS must pass through the Golgi membrane, which is facilitated by Golgi-resident transporters. Caenorhabditis elegans transporters are encoded two genes, pst-1 and pst-2. Using yeast heterologous expression system, we characterized PST-1 PST-2 as We created deletion mutants study importance transporter activity. The mutant exhibited defects in cuticle...
Chondroitin sulfate (CS)/chondroitin (Chn) chains are indispensable for embryonic cell division and cytokinesis in the early developmental stages Caenorhabditis elegans mice, whereas heparan (HS) is essential axon guidance during nervous system development. These data indicate that fundamental functions of CS HS conserved from worms to mammals function CS/Chn differs HS. Although previous studies have shown C. produces non-sulfated Chn, whether organism remains unclear. Here, we demonstrate...
Abstract RNA silencing signals in C. elegans spread among cells, leading to RNAi throughout the body. During systemic of RNAi, membrane trafficking is thought play important roles. Here, we show that Spreading Defective-3 ( rsd-3 ), which encodes a homolog epsinR, conserved ENTH (epsin N-terminal homology) domain protein, generally participates cellular uptake RNA. RSD-3 previously be involved only germ but isolated several deletion alleles , and found these mutants are defective not into...
Sulfation of biomolecules, which is widely observed from bacteria to humans, plays critical roles in many biological processes. All sulfation reactions all organisms require activated sulfate, 3′-phosphoadenosine 5′-phosphosulfate (PAPS), as a universal donor. In animals, PAPS synthesized ATP and inorganic sulfate by the bifunctional enzyme, synthase. mammals, genetic defects synthase 2, one two isozymes, cause dwarfism disorder, but little known about consequences complete loss synthesis....
Dietary supplied double-stranded RNA (dsRNA) can trigger interference (RNAi) systemically in some animals, including the nematode
In this study, we selected 181 nematode glycogenes that are orthologous to human and examined their RNAi phenotypes. The results deposited in the Caenorhabditis elegans Glycogene Database (CGGDB) at AIST, Tsukuba, Japan. most prominent phenotypes observed disruptions of cell cycle progression germline mitosis/meiosis early embryonic mitosis. Along with previously reported roles chondroitin proteoglycans, glycosphingolipids GPI-anchored proteins progression, show for first time inhibition...
硫酸化は生体分子の最も重要な修飾の一つであることが明らかとなり,バクテリアからヒトにいたる様々な生物の生体恒常性の維持や発生,形態形成などで重要な働きをしている。線虫 Caenorhabditis elegansには哺乳類の硫酸化関連遺伝子のほとんどのオーソログが存在しており,単一細胞レベルで硫酸化の働きを研究するための強力な研究手段として最適な生き物である。こうした硫酸化の詳細な解析をハエやマウスなど他のモデル生物で実施することはできない。このミニレビューでは,バイオインフォマティクスで選び出した,硫酸化関連遺伝子と予想される線虫遺伝子をリストアップして,既に私達や他の研究室で実施された遺伝子機能阻害実験(RNAi と遺伝子破壊株の取得による)の結果をまとめることとする。このユニークで優れたモデル生物を使った今後のさらなる研究によって,多細胞生物での硫酸化の重要な役割を批判的に検討する機会が得られると考えられる。
N-linked glycosylation of proteins is the most common post-translational modification proteins. The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses first step N-glycosylation, and DPAGT1 knockout embryonic lethal in mice. In this study, we identified sole orthologue (algn-7) human nematode C. elegans. gene activity was disrupted by RNAi deletion mutagenesis, which resulted larval lethality, defects oogenesis oocyte-to-embryo...
Abstract With the development of massive parallel sequencing technology, it has become easier to establish new model organisms that are ideally suited specific biological phenomena interest. Considering history research using classical organisms, we believe efficient construction and sharing gene mutation libraries will facilitate progress studies these organisms. Using C. elegans , applied TMP/UV mutagenesis method animals lacking function in DNA damage response genes atm-1 xpc-1 . This...
RNA interference (RNAi) is widely used in life science research and critical for diverse biological processes, such as germline development antiviral defense. In Caenorhabditis elegans , RNA-dependent polymerases, with redundant involvement of EGO-1 RRF-1, facilitate small amplification exogenous RNAi (exo-RNAi). However, their coordination during the regulation exo-RNAi processes remains unclear. Here, we examined non-null mutants ego-1 gene found that ego-1(S1198L) animals exhibited...