title: Mammalian septins are required for phagosome formation.
abstract: 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 FcgammaR-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 FcgammaR-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 genistein, 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 FcgammaR-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 FcgammaR-mediated phagocytosis.
authors.affiliation: Program in Cell Biology, Hospital for Sick Children, and Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Richard F
authors.initials: RF
authors.lastname: Collins
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Diciccio
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
authors.forename: William S
authors.initials: WS
authors.lastname: Trimble
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D058112:Septins; D014162:Transfection
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C080568:Fc gamma receptor IIA; D034741:RNA, Small Interfering; D017452:Receptors, IgG; D011994:Recombinant Proteins; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C496549:SEPTIN11 protein, human; C106863:Sept2 protein, mouse; C486672:Sept6 protein, mouse; D058112:Septins