Sphingomyelin synthase 1-generated sphingomyelin plays an important role in transferrin trafficking and cell proliferation

Abo Bakr Abdel Shakor, Makoto Taniguchi, Kazuyuki Kitatani, Mayumi Hashimoto, Satoshi Asano, Akira Hayashi, Kenichi Nomura, Jacek Bielawski, Alicja Bielawska, Ken Watanabe, Toshihide Kobayashi, Yasuyuki Igarashi, Hisanori Umehara, Hiroyuki Takeya, Toshiro Okazaki

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)36053-36062
Number of pages10
JournalJournal of Biological Chemistry
Issue number41
Publication statusPublished - 2011 Oct 14

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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