Cell surface colony-stimulating factor 1 can be cleaved by TNF-α converting enzyme or endocytosed in a clathrin-dependent manner

Keisuke Horiuchi, Takeshi Miyamoto, Hironari Takaishi, Akihiro Hakozaki, Naoto Kosaki, Yoshiteru Miyauchi, Mitsuru Furukawa, Jiro Takito, Hironori Kaneko, Kenichiro Matsuzaki, Hideo Morioka, Carl P. Blobel, Yoshiaki Toyama

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

CSF-1 is a hemopoietic growth factor, which plays an essential role in macrophage and osteoclast development. Alternative splice variants of CSF-1 are synthesized as soluble or membrane-anchored molecules, although membrane CSF-1 (mCSF-1) can be cleaved from the cell membrane to become soluble CSF-1. The activities involved in this proteolytic processing, also referred to as ectodomain shedding, remain poorly characterized. In the present study, we examined the properties of the mCSF-1 sheddase in cell-based assays. Shedding of mCSF-1 was up-regulated by phorbol ester treatment and was inhibited by the metalloprotease inhibitors GM6001 and tissue inhibitor of metalloproteases 3. Moreover, the stimulated shedding of mCSF-1 was abrogated in fibroblasts lacking the TNF-α converting enzyme (TACE, also known as a disintegrin and metalloprotease 17) and was rescued by expression of wild-type TACE in these cells, strongly suggesting that the stimulated shedding is TACE dependent. Additionally, we observed that mCSF-1 is predominantly localized to intracellular membrane compartments and is efficiently internalized in a clathrin-dependent manner. These results indicate that the local availability of mCSF-1 is actively regulated by ectodomain shedding and endocytosis. This mechanism may have important implications for the development and survival of monocyte lineage cells.

Original languageEnglish
Pages (from-to)6715-6724
Number of pages10
JournalJournal of Immunology
Volume179
Issue number10
Publication statusPublished - 2007 Nov 15

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Clathrin
Macrophage Colony-Stimulating Factor
Endocytosis
Enzymes
Membranes
Metalloproteases
Disintegrins
Intracellular Membranes
Phorbol Esters
Osteoclasts
Monocytes
Intercellular Signaling Peptides and Proteins
Fibroblasts
Macrophages
Cell Membrane

ASJC Scopus subject areas

  • Immunology

Cite this

Horiuchi, K., Miyamoto, T., Takaishi, H., Hakozaki, A., Kosaki, N., Miyauchi, Y., ... Toyama, Y. (2007). Cell surface colony-stimulating factor 1 can be cleaved by TNF-α converting enzyme or endocytosed in a clathrin-dependent manner. Journal of Immunology, 179(10), 6715-6724.

Cell surface colony-stimulating factor 1 can be cleaved by TNF-α converting enzyme or endocytosed in a clathrin-dependent manner. / Horiuchi, Keisuke; Miyamoto, Takeshi; Takaishi, Hironari; Hakozaki, Akihiro; Kosaki, Naoto; Miyauchi, Yoshiteru; Furukawa, Mitsuru; Takito, Jiro; Kaneko, Hironori; Matsuzaki, Kenichiro; Morioka, Hideo; Blobel, Carl P.; Toyama, Yoshiaki.

In: Journal of Immunology, Vol. 179, No. 10, 15.11.2007, p. 6715-6724.

Research output: Contribution to journalArticle

Horiuchi, K, Miyamoto, T, Takaishi, H, Hakozaki, A, Kosaki, N, Miyauchi, Y, Furukawa, M, Takito, J, Kaneko, H, Matsuzaki, K, Morioka, H, Blobel, CP & Toyama, Y 2007, 'Cell surface colony-stimulating factor 1 can be cleaved by TNF-α converting enzyme or endocytosed in a clathrin-dependent manner', Journal of Immunology, vol. 179, no. 10, pp. 6715-6724.
Horiuchi K, Miyamoto T, Takaishi H, Hakozaki A, Kosaki N, Miyauchi Y et al. Cell surface colony-stimulating factor 1 can be cleaved by TNF-α converting enzyme or endocytosed in a clathrin-dependent manner. Journal of Immunology. 2007 Nov 15;179(10):6715-6724.
Horiuchi, Keisuke ; Miyamoto, Takeshi ; Takaishi, Hironari ; Hakozaki, Akihiro ; Kosaki, Naoto ; Miyauchi, Yoshiteru ; Furukawa, Mitsuru ; Takito, Jiro ; Kaneko, Hironori ; Matsuzaki, Kenichiro ; Morioka, Hideo ; Blobel, Carl P. ; Toyama, Yoshiaki. / Cell surface colony-stimulating factor 1 can be cleaved by TNF-α converting enzyme or endocytosed in a clathrin-dependent manner. In: Journal of Immunology. 2007 ; Vol. 179, No. 10. pp. 6715-6724.
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