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MBC in Press, published online ahead of print February 13, 2008
Mol. Biol. Cell 10.1091/mbc.E07-07-0641

A more recent version of this article appeared on April 1, 2008
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Submitted on July 9, 2007
Revised on December 27, 2007
Accepted on January 30, 2008

Mammalian Septins are Required for Phagosome Formation

Yi-Wei Huang, Ming Yan, Richard F. Collins, Jessica E. DiCiccio, Sergio Grinstein, and William S. Trimble

Program in Cell Biology, Hospital for Sick Children, and Department of Biochemistry, University of Toronto, Toronto, Canada M5G1X8

Monitoring Editor: Erika Holzbaur

Septins are members of a highly conserved family of filamentous proteins that are required in many organisms for the completion of cytokinesis. In addition, septins have been implicated in a number of important cellular processes and have been suggested to have roles in regulating membrane traffic. Given the proposed role of septins in cell membrane dynamics, we investigated the function of septins during Fc{gamma}R-mediated phagocytosis. We show that several septins are expressed in RAW264.7 and J774 mouse macrophage cell lines, and that SEPT2 and SEPT11 are colocalized with submembranous actin-rich structures during the early stages of Fc{gamma}R-mediated phagocytosis. In addition, SEPT2 accumulation is seen in primary human neutrophils and in nonprofessional phagocytes. The time course of septin accumulation mirrors actin accumulation and is inhibited by latrunculin and genestein, but not other inhibitors of phagocytosis. Inhibition of septin function by transient expression of the BD3 domain of BORG3, known to cause septin aggregation, or depletion of SEPT2 or SEPT11 by RNAi, significantly inhibited Fc{gamma}R-mediated phagocytosis of IgG-coated latex beads. Interestingly, this occurred without affecting the accumulation of actin or the actin-associated protein coronin-1. These observations show that, although not necessary for actin recruitment, septins are required for efficient Fc{gamma}R-mediated phagocytosis.


Address correspondence to: William S. Trimble (wtrimble{at}sickkids.ca)







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