title: Tyrosine Phosphorylation of an Actin-Binding Protein Girdin Specifically Marks Tuft Cells in Human and Mouse Gut.
abstract: Tuft cells (TCs) are minor components of gastrointestinal epithelia, characterized by apical tufts and spool-shaped somas. The lack of reliable TC-markers has hindered the elucidation of its role. We developed site-specific and phosphorylation-status-specific antibodies against Girdin at tyrosine-1798 (pY1798) and found pY1798 immunostaining of mouse jejunum clearly depicted epithelial cells closely resembling TCs. This study aimed to validate pY1798 as a TC-marker. Double-fluorescence staining of intestines was performed with pY1798 and known TC-markers, for example, hematopoietic-prostaglandin-D-synthase (HPGDS), or doublecortin-like kinase 1 (DCLK1). Odds ratios (ORs) were calculated from cell counts to determine whether two markers were attracting (OR<1) or repelling (OR>1). In consequence, pY1798 signals strongly attracted those of known TC-markers. ORs for HPGDS in mouse stomach, small intestine, and colon were 0 for all, and 0.08 for DCLK1 in human small intestine. pY1798-positive cells in jejunum were distinct from other minor epithelial cells, including goblet, Paneth, and neuroendocrine cells. Thus, pY1798 was validated as a TC-marker. Interestingly, apoptosis inducers significantly increased relative TC frequencies despite the absence of proliferation at baseline. In conclusion, pY1798 is a novel TC-marker. Selective tyrosine phosphorylation and possible resistance to apoptosis inducers implied the activation of certain kinase(s) in TCs, which may become a clue to elucidate the enigmatic roles of TCs. .
authors.affiliation: Department of Pathology (DK, KU, SM, AE, NA, MT, MA), Nagoya University Graduate School of Medicine, Nagoya, Japan.|Division of Surgical Oncology, Department of Surgery (DK, MN), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kuga
authors.affiliation: Department of Pathology (DK, KU, SM, AE, NA, MT, MA), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ushida
authors.affiliation: Department of Pathology (DK, KU, SM, AE, NA, MT, MA), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Mii
authors.affiliation: Department of Pathology (DK, KU, SM, AE, NA, MT, MA), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.affiliation: Department of Pathology (DK, KU, SM, AE, NA, MT, MA), Nagoya University Graduate School of Medicine, Nagoya, Japan.|Division of Molecular Pathology, Center for Neurological Disease and Cancer (NA, MT), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Asai
authors.affiliation: Division of Surgical Oncology, Department of Surgery (DK, MN), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
authors.affiliation: Department of Pathology (DK, KU, SM, AE, NA, MT, MA), Nagoya University Graduate School of Medicine, Nagoya, Japan.|Division of Molecular Pathology, Center for Neurological Disease and Cancer (NA, MT), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Pathology (DK, KU, SM, AE, NA, MT, MA), Nagoya University Graduate School of Medicine, Nagoya, Japan.|Department of Endocrinology and Diabetes (MA), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Asai
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008840:Microfilament Proteins; D014443:Tyrosine; D033921:Vesicular Transport Proteins; C502451:CCDC88A protein, human; C527550:Ccdc88a protein, mouse
keywords: Girdin; brush cell; tuft cell marker; tyrosine phosphorylation