title: POT1b regulates phagocytosis and NO production by modulating activity of the small GTPase Rab5.
abstract: The protection of telomeres 1 (POT1) protein is a 75-kDa protein that plays an important role in telomere protection, which is related to telomere elongation. Although POT1 is present in and acts in the nuclei, little is known about the functions of POT1 in the cytosol. We here examined the role of POT1b in phagocytosis in a macrophage-like RAW 264 cell line. We found that POT1 was present in the cytosol, where it was bound to Rab5, which is a protein important for endocytosis. POT1b knockdown in RAW 264 cells increased Rab5 activity and facilitated the phagocytosis of whole cells of Escherichia coli and Staphylococcus aureus. Furthermore, POT1b knockdown enhanced the expression of inducible nitric oxide synthase (iNOS), followed by the promotion of nitric oxide (NO) generation in response to stimulation by bacterial whole cells. These results suggest that POT1b negatively regulates phagocytosis by controlling Rab5 activity and thereby modulates bacteria-induced NO generation. These findings suggest that POT1b participates in innate immune responses.
authors: Department of Oral Disease Research, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu, Aichi, Japan.
authors: Makoto
authors: M
authors: Hagiwara
authors: Toshinori
authors: T
authors: Komatsu
authors: Shin-suke
authors: SS
authors: Sugiura
authors: Ryutaro
authors: R
authors: Isoda
authors: Hiroyuki
authors: H
authors: Tada
authors: Naomi
authors: N
authors: Tanigawa
authors: Yoshiko
authors: Y
authors: Kato
authors: Naoyuki
authors: N
authors: Ishida
authors: Kaoru
authors: K
authors: Kobayashi
authors: Kenji
authors: K
authors: Matsushita
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000502:physiology; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D009569:Nitric Oxide / Q000276:immunology*; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000502:physiology; D020696:rab5 GTP-Binding Proteins / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; C512707:POT1b protein, mouse; D009569:Nitric Oxide; D020696:rab5 GTP-Binding Proteins
keywords: EEA1; GAP; GFP; GTPase-activating protein; IgG-HRP; Inflammation; NO; NOS; Nitric oxide; PBS; POT1b; Phagocytosis; Rab5; early endosome antigen 1; green fluorescence protein; iNOS; immunoglobulin G-horseradish peroxidase; inducible NOS; nitric oxide; nitric oxide synthase; phosphate-buffered saline; protection of telomeres 1b