Please use this identifier to cite or link to this item: 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
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