1995 Fiscal Year Final Research Report Summary
MODULATION OF BLOOD-BRAIN BARRIER
| Project/Area Number |
06557014
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | KYOTO UNIVERSITY (1995)
Okazaki National Research Institutes (1994) |
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Principal Investigator |
TSUKITA Shoichiro KYOTO UNIVERSITY,FACULTY OF MEDICINE PROFESSOR, 医学研究科, 教授 (50155347)
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| Co-Investigator(Kenkyū-buntansha) |
YONEMURA Shigenobu KYOTO UNIVERSITY,FACULTY OF MEDICINE LECUTURER, 医学研究科, 講師 (60192811)
ITOH Masahiko KYOUTO UNIVERSITY,FACULTY OF MEDICINE ASSISTANT, 医学研究科, 助手 (70270486)
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| Project Period (FY) |
1994 – 1995
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| Keywords | blood-brain barrier / tight junction / occludin / claudin / knock-out / cell adhesion / phosphrylation / endothelial cell |
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| Research Abstract |
To modulate the blood-brain barrier, i.e.tight junctions, we analyzed the functions of occludin. Occludin is the only known integral membrane protein of tight junctions (TJ), and is now believed to be directly involved in the barrier and fence functions of TJ.Occludin-deficient embryonic stem (ES) cells were generated by targeted disruption of both alleles of the occludin gene. When these cells were subjected to suspension culture, they aggregated to form simple, and then cystic embryoid bodies (EBs) with the same time course as EB formation from wild-type ES cells. Immunofluorescence microscopy and ultrathin section electron microscopy revealed that polarized epithelial (visceral endoderm-like) cells were differentiated to delineate EBs not only from wild-type but also from occludin-deficient ES cells. Freeze fracture analyzes indicated no significant differences in number or morphology of TJ strands between wild-type and occludin-deficient epithelial cells. Furthermore, ZO-1, a TJ-associated peripheral membrane protein, was still exclusively concentrated at TJ in occludin-deficient epithelial cells. In good agreement with these morphological observations, TJ in occludin-deficient epithelial cells functioned as a primary barrier to the diffusion of a low molecular mass tracer through the paracellular pathway. These findings indicate that there are as yet unidentified TJ integral membrane protein(s) which can form strand structures, recruit ZO-1, and function as a barrier without occludin.
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Research Products
(12 results)
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[Publications] Furuse, M., Fujimoto, K., Sato, N., Hirase, T., Tsukita, and Tsukita, Sh: "Overexpression of occludin,a tight junction associated integral membrane protein,induces the formation of intracellular multilamellar bodies bearing tight junction-like structures" J.Cell Sci.109. 429-435 (1996)
Description
「研究成果報告書概要(和文)」より
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[Publications] Ando-Akatsuka, Y., Saitou, M., Hirase, T., Kishi, M., Sakakibara, A., Itoh, M., Yonemura, S., Furuse, M., Tsukita, Sh: "Interspecies diversity of the occludin sequence:cDNA cloning of human,mouse,dog and rat-kangaroo:homologues" J.Cell Biol.133. 43-47 (1996)
Description
「研究成果報告書概要(和文)」より
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[Publications] Saitou, M., Akatsuka-Ando, Y., Itoh, M., Furuse, M., Inazawa, J., Fujimoto, K., and Tsukita, Sh: "Mammalian occludin in epithelial cells:Its expression and subcellular distribution" Eur.J.Cell Biol.73. 222-231 (1997)
Description
「研究成果報告書概要(和文)」より
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[Publications] Furuse, M., Itoh, M., Hirase, T., Nagafuchi, A., Yonemura, S., Tsukita, Sa., and Tsukita, Sh.: "Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions." J.Cell Biol.127. 1617-1626 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Takeda, H., Nagafuchi, A., Yonemura, S., Tsukita, Sa., Behrens, J., Birchimeier, W.and Tsukita, Sh.: "V-src kinase shifts the cadherin-based cell adhesion from the strong to the weak state and beta-catenin is not required for the shift." J.Cell Biol.131. 1839-1847 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Furuse, M., Fujimoto, K., Sato, N., Hirase, T., Tsukita, Sa., and Tsukita, Sh.: "Overexpression of occludin, a tight junction-associated integral membrane protein, induces the formation of intracellular multilamellar bodies bearing tight junction-like structures." J.Cell Sci.109. 429-435 (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ando-Akatsuka, Y., Saitou, M., Hirase, T., Kishi, M., Sakakibara, A., Itoh, M., Yonemura, S., Furuse, M., Tsukita, Sh.: "Interspecies diversity of the occludin sequence : cDNA cloning of human, mouse, dog and rat-kangaroo homologues" J.Cell Biol.133. 43-47 (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Saitou, M., Akatsuka-Ando, Y., Itoh, M., Furuse, M., Inazawa, J., Fujmoto, K., and Tsukita, Sh.: "Mammalian occludin in epithelial cells : Its expression and subcellular distribution" Eur.J.Cell Biol.73. 222-231 (1997)
Description
「研究成果報告書概要(欧文)」より
