Hiroshi Nakato, PhD

Research Techniques:

Molecular Genetics, Confocal microscopy

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.

Selected Publications:

Dejima, K., Kanai, M.I., Akiyama, T., Levings, D., and Nakato, H. (2011) Novel contact-dependent bone morphogenetic protein (BMP) signaling mediated by heparan sulfate proteoglycans.  J. Biol. Chem. 286, 17103-17111.

Kamimura, K., Maeda, N., and Nakato, H. (2011) In vivo manipulation of heparan sulfate structure and its effect on Drosophila development.  Glycobiology 21, 607-618.

Kleinschmit, A., Koyama, T., Dejima, K., Hayashi, Y., Kamimura, K., and Nakato H. (2010) Drosophila heparan sulfate 6-O endosulfatase regulates Wingless morphogen gradient formation.  Dev. Biol. 345, 204-214.

Hayashi, Y., Kobayashi, S., and Nakato, H. (2009) Drosophila glypicans regulate the germline stem cell niche.  J. Cell Biol. 187, 473-480.

Akiyama, T., Kamimura K., Firkus, C., Takeo, S., Shimmi, O., and Nakato, H. (2008) Dally regulates Dpp morphogen gradient formation by stabilizing Dpp on the cell surface. Dev. Biol. 313, 408-419.

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

 

To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
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