| 1. |
Fumiko Matsuzaki, Shinsuke Uda, Yukiyo Yamauchi, Masaki Matsumoto, Tomoyoshi Soga, Kazumitsu Maehara, Yasuyuki Ohkawa, Keiichi I Nakayama, Shinya Kuroda, Hiroyuki Kubota, An extensive and dynamic trans-omic network illustrating prominent regulatory mechanisms in response to insulin in the liver., Cell reports, 10.1016/j.celrep.2021.109569, 36, 8, 109569-109569, 2021.08, An effective combination of multi-omic datasets can enhance our understanding of complex biological phenomena. To build a context-dependent network with multiple omic layers, i.e., a trans-omic network, we perform phosphoproteomics, transcriptomics, proteomics, and metabolomics of murine liver for 4 h after insulin administration and integrate the resulting time series. Structural characteristics and dynamic nature of the network are analyzed to elucidate the impact of insulin. Early and prominent changes in protein phosphorylation and persistent and asynchronous changes in mRNA and protein levels through non-transcriptional mechanisms indicate enhanced crosstalk between phosphorylation-mediated signaling and protein expression regulation. Metabolic response shows different temporal regulation with transient increases at early time points across categories and enhanced response in the amino acid and nucleotide categories at later time points as a result of process convergence. This extensive and dynamic view of the trans-omic network elucidates prominent regulatory mechanisms that drive insulin responses through intricate interlayer coordination.. |
| 2. |
Michiko Shirane, Mariko Wada, Keiko Morita, Nahoki Hayashi, Reina Kunimatsu, Yuki Matsumoto, Fumiko Matsuzaki, Hirokazu Nakatsumi, Keisuke Ohta, Yasushi Tamura, Keiichi I Nakayama, Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation, Nature communications, 10.1038/s41467-020-18413-9, 11, 1, 4576, 2020.09, Endosome maturation depends on membrane contact sites (MCSs) formed between endoplasmic reticulum (ER) and endolysosomes (LyLEs). The mechanism underlying lipid supply for this process and its pathophysiological relevance remains unclear, however. Here, we identify PDZD8-the mammalian ortholog of a yeast ERMES subunit-as a protein that interacts with protrudin, which is located at ER-LyLE MCSs. Protrudin and PDZD8 promote the formation of ER-LyLE MCSs, and PDZD8 shows the ability to extract various lipids from the ER. Overexpression of both protrudin and PDZD8 in HeLa cells, as well as their depletion in mouse primary neurons, impairs endosomal homeostasis by inducing the formation of abnormal large vacuoles reminiscent of those apparent in spastin- or REEP1-deficient neurons. The protrudin-PDZD8 system is also essential for the establishment of neuronal polarity. Our results suggest that protrudin and PDZD8 cooperatively promote endosome maturation by mediating ER-LyLE tethering and lipid extraction at MCSs, thereby maintaining neuronal polarity and integrity.. |
| 3. |
Osamu Maruyama, Fumiko Matsuzaki, DegSampler3
Pairwise dependency model in degradation motif site prediction of substrate protein sequences, 19th International Conference on Bioinformatics and Bioengineering, BIBE 2019
Proceedings - 2019 IEEE 19th International Conference on Bioinformatics and Bioengineering, BIBE 2019, 10.1109/BIBE.2019.00012, 11-17, 2019.10, In the ubiquitin-proteasome system, E3 ubiquitin ligase (E3s for short) selectively recognize and bind specific regions of their substrate proteins. Sequence motifs whose sites are bound by E3 ubiquitin ligases are called degrons. Because much remains unclear about the relationship between substrate proteins of E3s and their binding sites, there is a need to computationally identify such binding sites from the substrate proteins. For this motif identification problem, in our previous works, we have proposed a series of collapsed Gibbs sampling algorithms, called DegSampler1 and DegSampler2, both of which use position-specific prior information. In this work, we propose a new collapsed Gibbs sampling algorithm, called DegSampler3, by integrating intra-motif pair-wise dependency model into the posterior probability distribution of DegSampler2. In our preliminary experiments, we found that DegSampler3 has the ability of finding more various degron sites than DegSampler2 while keeping the prediction accuracy almost the same as that of the previous method, DegSampler2.. |
| 4. |
Osamu Maruyama, Fumiko Matsuzaki, DegSampler
Collapsed Gibbs sampler for detecting E3 binding sites, 18th IEEE International Conference on Bioinformatics and Bioengineering, BIBE 2018
Proceedings - 2018 IEEE 18th International Conference on Bioinformatics and Bioengineering, BIBE 2018, 10.1109/BIBE.2018.00009, 1-9, 2018.12, In this paper, we address the problem of finding sequence motifs in substrate proteins specific to E3 ubiquitin ligases (E3s). We formulated a posterior probability distribution of sites by designing a likelihood function based on amino acid indexing and a prior distribution based on the disorderness of protein sequences. These designs are derived from known characteristics of E3 binding sites in substrate proteins. Then, we devise a collapsed Gibbs sampling algorithm for the posterior probability distribution called DegSampler. We performed computational experiments using 36 sets of substrate proteins specific to E3s and compared the performance of DegSampler with those of popular motif finders, MEME and GLAM2. The results showed that DegSampler was superior to the others in finding E3 binding motifs. Thus, DegSampler is a promising tool for finding E3 motifs in substrate proteins.. |
| 5. |
Kiyota Sakai, Fumiko Matsuzaki, Lisa Wise, Yu Sakai, Sadanari Jindou, Hirofumi Ichinose, Naoki Takaya, Masashi Kato, Hiroyuki Wariishi, Motoyuki Shimizu, Biochemical characterization of CYP505D6, a self-sufficient cytochrome P450 from the white-rot fungus Phanerochaete chrysosporium, Applied and Environmental Microbiology, 10.1128/AEM.01091-18, 84, 22, 2018.11, The activity of a self-sufficient cytochrome P450 enzyme, CYP505D6, from the lignin-degrading basidiomycete Phanerochaete chrysosporium was characterized. Recombinant CYP505D6 was produced in Escherichia coli and purified. In the presence of NADPH, CYP505D6 used a series of saturated fatty alcohols with C9-18 carbon chain lengths as the substrates. Hydroxylation occurred at the ω-1 to ω-6 positions of such substrates with C9-15 carbon chain lengths, except for 1-dodecanol, which was hydroxylated at the ω-1 to ω-7 positions. Fatty acids were also substrates of CYP505D6. Based on the sequence alignment, the corresponding amino acid of Tyr51, which is located at the entrance to the active-site pocket in CYP102A1, was Val51 in CYP505D6. To understand the diverse hydroxylation mechanism, wild-type CYP505D6 and its V51Y variant and wild-type CYP102A1 and its Y51V variant were generated, and the products of their reaction with dodecanoic acid were analyzed. Compared with wild-type CYP505D6, its V51Y variant generated few products hydroxylated at the ω-4 to ω-6 positions. The products generated by wild-type CYP102A1 were hydroxylated at the ω-1 to ω-4 positions, whereas its Y51V variant generated ω-1 to ω-7 hydroxydodecanoic acids. These observations indicated that Val51 plays an important role in determining the regiospecificity of fatty acid hydroxylation, at least that at the ω-4 to ω-6 positions. Aromatic compounds, such as naphthalene and 1-naphthol, were also hydroxylated by CYP505D6. These findings highlight a unique broad substrate spectrum of CYP505D6, rendering it an attractive candidate enzyme for the biotechnological industry.. |
| 6. |
Hiroyuki Kubota, Shinsuke Uda, Fumiko Matsuzaki, Yukiyo Yamauchi, Shinya Kuroda, In Vivo Decoding Mechanisms of the Temporal Patterns of Blood Insulin by the Insulin-AKT Pathway in the Liver, Cell Systems, 10.1016/j.cels.2018.05.013, 2018.07, Cells respond to various extracellular stimuli through a limited number of signaling pathways. One strategy to process such stimuli is to code the information into the temporal patterns of molecules. Although we showed that insulin selectively regulated molecules depending on its temporal patterns using Fao cells, the in vivo mechanism remains unknown. Here, we show how the insulin-AKT pathway processes the information encoded into the temporal patterns of blood insulin. We performed hyperinsulinemic-euglycemic clamp experiments and found that, in the liver, all temporal patterns of insulin are encoded into the insulin receptor, and downstream molecules selectively decode them through AKT. S6K selectively decodes the additional secretion information. G6Pase interprets the basal secretion information through FoxO1, while GSK3β decodes all secretion pattern information. Mathematical modeling revealed the mechanism via differences in network structures and from sensitivity and time constants. Given that almost all hormones exhibit distinct temporal patterns, temporal coding may be a general principle of system homeostasis by hormones. Kubota et al. show that the insulin-AKT pathway in the liver processes the information encoded into the temporal patterns of blood insulin and selectively regulates downstream molecules. Given that almost all hormones exhibit distinct temporal patterns, our study demonstrates the possibility of temporal coding as a general principle of systemic homeostasis by hormones.. |
| 7. |
Masaki Matsumoto, Fumiko Matsuzaki, Kiyotaka Oshikawa, Naoki Goshima, Masatoshi Mori, Yoshifumi Kawamura, Koji Ogawa, Eriko Fukuda, Hirokazu Nakatsumi, Tohru Natsume, Kazuhiko Fukui, Katsuhisa Horimoto, Takeshi Nagashima, Ryo Funayama, Keiko Nakayama, Keiichi Nakayama, A large-scale targeted proteomics assay resource based on an in vitro human proteome, NATURE METHODS, 10.1038/nmeth.4116, 14, 3, 251-258, 2017.03. |
| 8. |
Yutaka Hashimoto, Michiko Shirane, Fumiko Matsuzaki, Shotaro Saita, Takafumi Ohnishi, Keiichi Nakayama, Protrudin Regulates Endoplasmic Reticulum Morphology and Function Associated with the Pathogenesis of Hereditary Spastic Paraplegia, JOURNAL OF BIOLOGICAL CHEMISTRY, 10.1074/jbc.M113.528687, 289, 19, 12946-12961, 2014.05. |
| 9. |
Fumiko Matsuzaki, Michiko Shirane, Masaki Matsumoto, Keiichi Nakayama, Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation, MOLECULAR BIOLOGY OF THE CELL, 10.1091/mbc.E11-01-0068, 22, 23, 4602-4620, 2011.12. |
| 10. |
Fumiko Matsuzaki, Motoyuki Shimizu, Hiroyuki Wariishi, Proteomic and metabolomic analyses of the white-rot fungus Phanerochaete chrysosporium exposed to exogenous benzoic acid, JOURNAL OF PROTEOME RESEARCH, 10.1021/pr700617s, 7, 6, 2342-2350, 2008.06. |
| 11. |
Fumiko Matsuzaki, Hiroyuki Wariishi, Functional diversity of cytochrome P450s of the white-rot fungus Phanerochaete chrysosporium, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 10.1016/j.bbrc.2004.09.062, 324, 1, 387-393, 2004.11. |
| 12. |
Fumiko Matsuzaki, Hiroyuki Wariishi, Molecular characterization of cytochrome P450 catalyzing hydroxylation of benzoates from the white-rot fungus Phaherochaete chrysosporzum, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 10.1016/j.bbrc.2005.07.013, 334, 4, 1184-1190, 2005.09. |
