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Regulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages


Colony stimulating factor-1 (CSF-1) is the main growth factor controlling the development of macrophages from myeloid progenitor cells. However, CSF-1 also regulates some of the key effector functions of macrophages (e.g. phagocytosis and cytokine secretion). The endosomal SNARE protein syntaxin 7 (Stx7) regulates vesicle trafficking events involved in phagocytosis and cytokine secretion. Therefore, we investigated the ability of CSF-1 to regulate Stx7. CSF-1 up-regulated Stx7 expression in primary mouse macrophages; it also up-regulated expression of its SNARE partners Vti1b and VAMP8 but not Stx8. Additionally, CSF-1 induced the rapid serine phosphorylation of Stx7, and enhanced its binding to Vti1b, Stx8 and VAMP8. Bioinformatics analysis and results from experiments with kinase inhibitors suggested the CSF-1-induced phosphorylation of Stx7 was mediated by protein kinase C and Akt in response to PI3-kinase activation. Based on mutagenesis studies, CSF-1 appeared to increase the binding of Stx7 to its SNARE partners by inducing the phosphorylation of serine residues in the Habc domain and/or ""linker"" region of Stx7. Thus, CSF-1 is a key regulator of Stx7 expression and function in macrophages. Furthermore, the effects of CSF-1 on Stx7 may provide a mechanism for the regulation of macrophage effector functions by CSF-1.

Type Journal
ISBN 1098-5549
Authors Achuthan, A.; Masendycz, P.; Lopez, J. A.; Nguyen, T.; James, D. E.; Sweet, M. J.; Hamilton, J. A.; Scholz, G. M.
Published Date 2008-10-01
Published Volume 28
Published Issue 20
Published Pages 6149-59
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version