Kon, S. and Minegishi, N. and Tanabe, K. and Watanabe, T. and Funaki, T. and Wong, W.F. and Sakamoto, D. and Higuchi, Y. and Kiyonari, H. and Asano, K. and Iwakura, Y. and Fukumoto, M. and Osato, M. and Sanada, M. and Ogawa, S. and Nakamura, T. and Satake, M. (2013) Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia. The Journal of Clinical Investigation, 123 (3). pp. 1123-1137. ISSN 0021-9738, DOI https://doi.org/10.1172/JCI63711.
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Smap1; Deficiency; Perturbs; Receptor trafficking; Predisposes mice; Myelodysplasia |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 13 Mar 2015 02:34 |
| Last Modified: | 13 Mar 2015 02:34 |
| URI: | http://eprints.um.edu.my/id/eprint/13027 |
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