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Mol. Cell. Biol. doi:10.1128/MCB.00220-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Regulation of the Endosomal SNARE Protein Syntaxin 7 by Colony Stimulating Factor-1 in Macrophages

Department of Medicine and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Garvan Institute of Medical Research, Darlinghurst, 2010 Sydney, New South Wales, Australia; and Institute for Molecular Bioscience and Cooperative Research Centre for Chronic Inflammatory Diseases, University of Queensland, Brisbane, Queensland 4072, Australia

^* To whom correspondence should be addressed. Email: glenms{at}unimelb.edu.au.

	Abstract

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.