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Return to: College of Biological Sciences: Medical School: U of M Home |
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Areas of Research Strength: Proteoglycan functions in development Growth factor signaling Morphogen gradient formation back to top |
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Research Techniques: Molecular Genetics Confocal microscopy back to top |
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Research Interests: The Nakato Lab studies how cells communicate with each other during tissue assembly of multicellular organisms using the fruitfly, Drosophila as a model. The lab is particularly interested in elucidating the function of heparan sulfate proteoglycans (HSPGs) in development. HSPGs have been implicated in a wide variety of biological processes such as growth factor signaling, cell adhesion, wound healing, and tumor metastasis. The Nakato Lab is currently focusing on two major projects described below: 1) Proteoglycan functions in morphogen gradient formation A morphogen is a type of signaling molecule that specifies different cell fates in a concentration dependent manner. During pattern formation of the Drosophila wing, Wingless, Hedgehog, and Decapentaplegic have been shown to function as morphogens. Although the formation of morphogen gradients is an essential process for patterning and morphogenesis, the molecular mechanism of morphogen gradient formation remains largely a mystery. Recent studies have shown that HSPGs are involved in this process. The long-term goal of this project is to understand how HSPGs regulate secretion, movement, degradation, and signaling of morphogens to establish and maintain the gradient. 2) Heparan sulfate fine structure and specificity of HSPG functions Heparan sulfate chains have markedly heterogeneous structures in which distinct patterns of sulfation determine the binding specificity for ligand proteins. These ‘‘fine structures’’ of heparan sulfate are mainly produced by the regulated introduction of sulfate groups at the N-, 2-O-, 6-O-, and 3-O-positions of the sugar chain. Recent biochemical, histochemical, and genetic studies have demonstrated that different fine structures of HS mediate distinct molecular recognition events to regulate a variety of cellular functions. Another area of our interest is to learn the molecular basis of growth factor control by the sulfation status of heparan sulfate. back to top |
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Selected Publications: Kamimura, K., Koyama, T., Habuchi., H., Ueda, R., Masu, M., Kimata, K., and Nakato, H. (2006) Specific and flexible roles of heparan sulfate modifications in Drosophila FGF signaling. J. Cell Biol. 147, 773-778. Takeo, S., Akiyama, T., Firkus, C., Aigaki, T., and Nakato, H. (2005) Expression of a secreted form of Dally, a Drosophila glypican, induces overgrowth phenotype by affecting action range of Hedgehog. Dev. Biol. 284, 204-218. Kotani N, Kitazume S, Kamimura K, Takeo S, Aigaki T, Nakato H, and Hashimoto Y (2005). Drosophila orthologues of human B-secretase incuce the secretion of a Golgi-resident transferase, heparan sulfate 6-O-sulotransferase. J. Biochem. 137, 315-322. Adachi-Yamada, T., Harumoto, T., Sakurai, K., Ueda, R., Saigo, K., O'Connor, M.B., and Nakato, H. (2005) Wing-to-leg homeosis by Spineless causes an apoptosis regulated by Fish-lips, a novel leucine-rich repeats transmembrane protein. Mol. Cell. Biol. 25, 3140-3150 Kamimura K., Rhodes J.M., Ueda R., Kimata K., McNeely M., Shukla D., Spear P.G., Shworak N.W., and Nakato H. (2004) Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase. J. Cell Biol. 166, 1069-1079. Takeo S., Fujise, M., Akiyama, T., Habuchi, H., Itano, N., Matsuo, T., Aigaki, T., Kimata, K., and Nakato, H. (2004) In vivo hyaluronan synthesis upon expression of mammalian hyaluronan synthase gene in Drosophila. J. Biol. Chem. 279, 18920-18925. Selleck, S.B. and Nakato, H. (2004) Functional dissection of glycoconjugates during development: Lessons from the fruitfly. Trends Glycosci. Glycotech. 16, 95-108. Fujise, M. Takeo, S., Kamimura, K., Matsuo, T., Aigaki, T., Izumi, S. and Nakato, H. (2003) Dally regulates Dpp morphogen gradient formation in the Drosophila wing. Development 130, 1515-1522 Takemae, H., Ueda, R., Ohkubo, R., Nakato, H., Izumi, S., Saigo, K., and Nishihara, S. (2003) Proteoglycan UDP-galactose:beta-xylose beta1,4galactosyltransferase I is essential for viability in Drosophila melanogaster. J. Biol. Chem. 278, 15571-15578. Nakato, H., Fox, B., and Selleck, S.B. (2002) dally, a Drosophila member of the glypican family of integral membrane proteoglycans, affects cell cycle progression and morphogenesis via a Cyclin A-mediated process. J. Cell Sci. 115, 123-130. Nakato, H. (2002) Heparan sulfate proteoglycans in Drosophila morphogenesis. Connective Tissue, 34, 267-275. Nakato, H. and Kimata, K. (2002) Heparan sulfate fine structure and specificity of proteoglycan functions. Biochim. Biophys. Acta, 1573, 312-318. Fujise M., Izumi S., Selleck S.B., Nakato, H. (2001) Regulation of dally, an integral membrane proteoglycan, and its function during adult sensory organ formation of Drosophila. Dev. Biol. 235, 433-448. Tsuda M., Izumi S., Nakato H. (2001) Transcriptional and posttranscriptional regulation of the gene for Dally, a Drosophila integral membrane proteoglycan. FEBS Lett. 494, 241-245. Kamimura K., Fujise M., Villa F., Izumi S., Habuchi H., Kimata K., Nakato, H. (2001) Drosophila heparan sulfate 6-O-sulfotransferase (dHS6ST) gene: Structure, expression, and function in the formation of the tracheal system. J. Biol. Chem. 276, 17014-17021. To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed search menu should say PubMed type Nakato H in the avaliable line back to top |
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