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https://doi.org/10.1172/JCI63711
Title: | Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia | Authors: | Kon, S. Minegishi, N. Tanabe, K. Watanabe, T. Funaki, T. Wong, W.F. Sakamoto, D. Higuchi, Y. Kiyonari, H. Asano, K. Iwakura, Y. Fukumoto, M. Osato, M. Sanada, M. Ogawa, S. Nakamura, T. Satake, M. |
Issue Date: | 1-Mar-2013 | Citation: | Kon, S., Minegishi, N., Tanabe, K., Watanabe, T., Funaki, T., Wong, W.F., Sakamoto, D., Higuchi, Y., Kiyonari, H., Asano, K., Iwakura, Y., Fukumoto, M., Osato, M., Sanada, M., Ogawa, S., Nakamura, T., Satake, M. (2013-03-01). Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia. Journal of Clinical Investigation 123 (3) : 1123-1137. ScholarBank@NUS Repository. https://doi.org/10.1172/JCI63711 | Abstract: | The formation of clathrin-coated vesicles is essential for intracellular membrane trafficking between subcellular compartments and is triggered by the ARF family of small GTPases. We previously identified SMAP1 as an ARF6 GTPase-activating protein that functions in clathrin-dependent endocytosis. Because abnormalities in clathrin-dependent trafficking are often associated with oncogenesis, we targeted Smap1 in mice to examine its physiological and pathological significance. Smap1-deficent mice exhibited healthy growth, but their erythroblasts showed enhanced transferrin endocytosis. In mast cells cultured in SCF, Smap1 deficiency did not affect the internalization of c-KIT but impaired the sorting of internalized c-KIT from multivesicular bodies to lysosomes, resulting in intracellular accumulation of undegraded c-KIT that was accompanied by enhanced activation of ERK and increased cell growth. Interestingly, approximately 50% of aged Smap1-deficient mice developed anemia associated with morphologically dysplastic cells of erythroid-myeloid lineage, which are hematological abnormalities similar to myelodysplastic syndrome (MDS) in humans. Furthermore, some Smap1-deficient mice developed acute myeloid leukemia (AML) of various subtypes. Collectively, to our knowledge these results provide the first evidence in a mouse model that the deregulation of clathrin-dependent membrane trafficking may be involved in the development of MDS and subsequent AML. | Source Title: | Journal of Clinical Investigation | URI: | http://scholarbank.nus.edu.sg/handle/10635/110786 | ISSN: | 00219738 | DOI: | 10.1172/JCI63711 |
Appears in Collections: | Staff Publications |
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