RRC ID 6616
Author Hatsuzawa K, Hashimoto H, Hashimoto H, Arai S, Tamura T, Higa-Nishiyama A, Wada I.
Title Sec22b is a negative regulator of phagocytosis in macrophages.
Journal Mol Biol Cell
Abstract The endoplasmic reticulum (ER) is proposed to be a membrane donor for phagosome formation. In support of this, we have previously shown that the expression level of syntaxin 18, an ER-localized SNARE protein, correlates with phagocytosis activity. To obtain further insights into the involvement of the ER in phagocytosis we focused on Sec22b, another ER-localized SNARE protein that is also found on phagosomal membranes. In marked contrast to the effects of syntaxin 18, we report here that phagocytosis was nearly abolished in J774 macrophages stably expressing mVenus-tagged Sec22b, without affecting the cell surface expression of the Fc receptor or other membrane proteins related to phagocytosis. Conversely, the capacity of the parental J774 cells for phagocytosis was increased when endogenous Sec22b expression was suppressed. Domain analyses of Sec22b revealed that the R-SNARE motif, a selective domain for forming a SNARE complex with syntaxin18 and/or D12, was responsible for the inhibition of phagocytosis. These results strongly support the ER-mediated phagocytosis model and indicate that Sec22b is a negative regulator of phagocytosis in macrophages, most likely by regulating the level of free syntaxin 18 and/or D12 at the site of phagocytosis.
Volume 20(20)
Pages 4435-43
Published 2009-10
DOI 10.1091/mbc.e09-03-0241
PII E09-03-0241
PMID 19710423
PMC PMC2762144
MeSH Amino Acid Motifs Animals Cell Line Endoplasmic Reticulum / metabolism Humans Macrophages / physiology* Mice Opsonin Proteins / metabolism Phagocytosis / physiology* Protein Interaction Mapping Protein Structure, Tertiary Qa-SNARE Proteins / chemistry Qa-SNARE Proteins / physiology* Qc-SNARE Proteins / chemistry Qc-SNARE Proteins / physiology* R-SNARE Proteins / chemistry R-SNARE Proteins / physiology* RNA, Small Interfering / pharmacology Receptors, IgG / metabolism Recombinant Fusion Proteins / physiology SNARE Proteins / chemistry SNARE Proteins / physiology* Zymosan / metabolism
IF 3.905
Times Cited 25
Human and Animal Cells