RRC ID 42676
Author Hatsuzawa K, Tamura T, Hashimoto H, Hashimoto H, Yokoya S, Miura M, Nagaya H, Wada I.
Title Involvement of syntaxin 18, an endoplasmic reticulum (ER)-localized SNARE protein, in ER-mediated phagocytosis.
Journal Mol Biol Cell
Abstract The endoplasmic reticulum (ER) is thought to play an important structural and functional role in phagocytosis. According to this model, direct membrane fusion between the ER and the plasma or phagosomal membrane must precede further invagination, but the exact mechanisms remain elusive. Here, we investigated whether various ER-localized SNARE proteins are involved in this fusion process. When phagosomes were isolated from murine J774 macrophages, we found that ER-localized SNARE proteins (syntaxin 18, D12, and Sec22b) were significantly enriched in the phagosomes. Fluorescence and immuno-EM analyses confirmed the localization of syntaxin 18 in the phagosomal membranes of J774 cells stably expressing this protein tagged to a GFP variant. To examine whether these SNARE proteins are required for phagocytosis, we generated 293T cells stably expressing the Fc gamma receptor, in which phagocytosis occurs in an IgG-mediated manner. Expression in these cells of dominant-negative mutants of syntaxin 18 or D12 lacking the transmembrane domain, but not a Sec22b mutant, impaired phagocytosis. Syntaxin 18 small interfering RNA (siRNA) selectively decreased the efficiency of phagocytosis, and the rate of phagocytosis was markedly enhanced by stable overexpression of syntaxin 18 in J774 cells. Therefore, we conclude that syntaxin 18 is involved in ER-mediated phagocytosis, presumably by regulating the specific and direct fusion of the ER and plasma or phagosomal membranes.
Volume 17(9)
Pages 3964-77
Published 2006-9-1
DOI 10.1091/mbc.e05-12-1174
PII E05-12-1174
PMID 16790498
PMC PMC1593171
MeSH Amino Acid Sequence Animals Antigens, CD / immunology COP-Coated Vesicles / metabolism Cell Membrane / metabolism Cells, Cultured Endoplasmic Reticulum / metabolism* Gene Expression Humans Macrophages / cytology Macrophages / ultrastructure Mice Molecular Sequence Data Oligopeptides Peptides / metabolism Phagocytosis / physiology* Phagosomes / ultrastructure Protein Binding Protein Structure, Tertiary Protein Transport Qa-SNARE Proteins / chemistry Qa-SNARE Proteins / metabolism* R-SNARE Proteins / metabolism RNA, Small Interfering Receptors, IgG / immunology
IF 3.791
Times Cited 65
Human and Animal Cells J774.1(RCB0434)