| Project/Area Number |
16390319
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
JIMBOW Kowichi Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (30094238)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Toshiharu Sapporo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (50167706)
KOKAI Yasuo Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (20178239)
SOHMA Hitoshi Sapporo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (70226702)
SAKANE Fumio Sapporo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (10183815)
HIROSAKI Kuninori Sapporo Medical University, School of Medicine, Instructor, 医学部, 助手 (00363705)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | Melanin / Melanosome / Melanocyte / Transgene / GTP-binding protein / Pigmentation Disorder / Transgenic mouse / Rab7 / トランスジーン / 低分子G蛋白 / トランスジェニックマウス / Rab蛋白 |
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| Research Abstract |
This study characterizes the interrelationship between alteration of melanosome biosynthesis and functional failure of organs in man. The rationale behind this proposal is that there are marked similarities between melanosomes and lysosomes. This study characterizes the interrelationship between the biosynthesis of melanosomes and lysosomes and their functional roles in man. The rationale behind this proposal is that there exists a marked similarity in the biosynthesis processes between melanosomes and lysosomes, i.e., the two granules are present in acidic compartments and share many common biosynthesis processes such as vesicular transport from trans Golgi network (TGN). Melanosomes are made of glycoproteins, which consist of tyrosinase, tyrosinase-related proteins (TYRPs) and structural gp100 protein. Among these melanosomal proteins TYRP1 is the most abundant one. Our previous studies indicated (1) that the stage I melanosomes derive from endosomal granules such as early and late e
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ndosomes, (2) that melanosomal compartments are associated with cation independent-mannose 6 phosphate receptor (CI-M6PR) and regulated by ADP-ribosylation factor (ARF), and (3) that Rab7 (small GTP-binding protein) plays a key role in transport of TYRP1 from TGN to early melanosomes. In this project we wish to characterize the vesicular transport in the biosynthesis processes of acidic endosomal, lysosomal granules of melanosomes and their biological roles in man by utilizing transgenic mouse system.
We found (1) that the inhibition of Rab7 function resulted in preferential TYRP1 elimination from melanocytes due to proteasomal degradation, (2) that endogenous and exogenous TYRP1 is co-immunoprecipitated with adaptin 1(AP1), (3) that the interaction between TYRP1 and AP1 is present in early stage of the TGN-derived vesicular transport, and (4) that Flag-tagged wt TYRP1 is co-localized with AP1, MGPR and GGA3. We also succeeded in establishing dominant/negative Rab7 transgenic mice, but are not yet successful in identifying visual pigmentation defects in these mice. Less
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