2012 Fiscal Year Final Research Report
Dysregulation of clathrin-dependent traffic causes hematopoietic neoplasm
| Project/Area Number |
23770137
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
SHUNSUKE Kon 東北大学, 加齢医学研究科, 助教 (70506641)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 細胞内小胞輸送 / SMAP1 / 骨髄異形成症候群 / 白血病 |
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| Research Abstract |
Approximately 50% of aged SMAP1(-/-) mice developed anemia associated with morphologically dysplastic cells of erythroid-myeloid lineage, which are hematological abnormalities reminiscent of those seen in myelodysplastic syndrome (MDS) in humans. Furthermore, some SMAP1(-/-) mice developed acute myeloid leukemia (AML) of various subtypes. The transport analysis showed that transferrin endocytosis was enhanced in erythroblasts of SMAP1(-/-) mice. In mast cells cultured in stem cell factor, SMAP1 deficiency did not affect the internalization of c-Kit but impaired the sorting of internalized c-Kit from multivesicular bodies to lysosomes, which caused the intracellular accumulation of undegraded c-Kit accompanied by a significant increase in ERK phosphorylation and cell growth activity. Collectively, these results provide the first evidence in a mouse model that the deregulation of clathrin-dependent membrane trafficking involving the transferrin receptor and c-Kit may be involved inthe development of MDS and subsequent AML.
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[Journal Article] deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia2013
Author(s)
Kon, S., Minegishi, N., Tanabe, K., Watanabe, T., Funaki, T., Wong, WF., Sakamoto, D., Higuchi, Y., Kiyonari, H., Asano, K., Iwakura, Y., Fukumoto, M., Osato, M., Sanada, S., Ogawa, S., Nakamura, T and Satake, M. Smap1
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Journal Title
J. Clin. Invest
Volume: 123
Pages: 1123-1137
DOI
Peer Reviewed
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