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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Sphingomyelin synthase 1-generated sphingomyelin plays an important role in transferrin trafficking and cell proliferation
Journal of Biological Chemistry, Volume 286, No. 41, Year 2011
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Description
Transferrin (Tf) endocytosis and recycling are essential for iron uptake and the regulation of cell proliferation. Tf and Tf receptor (TfR) complexes are internalized via clathrin-coated pits composed of a variety of proteins and lipids and pass through early endosomes to recycling endosomes. We investigated the role of sphingomyelin (SM) synthases (SMS1 and SMS2) in clathrin-dependent trafficking of Tf and cell proliferation. We employed SM-deficient lymphoma cells that lacked SMSs and that failed to proliferate in response to Tf. Transfection of SMS1, but not SMS2, enabled these cells to incorporate SM into the plasma membrane, restoring Tf-mediated proliferation. SM-deficient cells showed a significant reduction in clathrin-dependent Tf uptake compared with the parental SM producing cells. Both SMS1 gene transfection and exogenous short-chain SM treatment increased clathrin-dependent Tf uptake in SM-deficient cells, with the Tf being subsequently sorted to Rab11-positive recycling endosomes. We observed trafficking of the internalized Tf to late/endolysosomal compartments, and this was not dependent on the clathrin pathway in SM-deficient cells. Thus, SMS1-mediated SM synthesis directs Tf-TfR to undergo clathrin-dependent endocytosis and recycling, promoting the proliferation of lymphoma cells. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Authors & Co-Authors
Shakor, Abo Bakr Abdel
Japan, Yonago
Tottori University Faculty of Medicine
Egypt, Asiut
Faculty of Science
Taniguchi, Makoto
Japan, Yonago
Tottori University Faculty of Medicine
Kitatani, Kazuyuki
Japan, Yonago
Tottori University Faculty of Medicine
Hashimoto, Mayumi
Japan, Yonago
Tottori University Faculty of Medicine
Asano, Satoshi
Japan, Yonago
Tottori University Faculty of Medicine
Hayashi, Akira
Japan, Yonago
Tottori University Faculty of Medicine
Nomura, Kenichi
Japan, Yonago
Tottori University Faculty of Medicine
Bielawski, Jacek
United States, Charleston
Medical University of South Carolina
Bielawska, Alicja
United States, Charleston
Medical University of South Carolina
Watanabe, Ken
Japan, Obu
National Center for Geriatrics and Gerontology
Kobayashi, Toshihide
Japan, Wako
Riken
Igarashi, Yasuyuki
Japan, Sapporo
Hokkaido University
Umehara, Hisanori
Japan, Kahoku
Kanazawa Medical University
Takeya, Hiroyuki
Japan, Tottori
Tottori University
Okazaki, Toshiro
Japan, Yonago
Tottori University Faculty of Medicine
Japan, Kahoku
Kanazawa Medical University
Statistics
Citations: 61
Authors: 15
Affiliations: 8
Identifiers
Doi:
10.1074/jbc.M111.228593
ISSN:
00219258
e-ISSN:
1083351X
Research Areas
Genetics And Genomics