title: SNAP23 is selectively expressed in airway secretory cells and mediates baseline and stimulated mucin secretion.
abstract: Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23 (23-kDa paralogue of synaptosome-associated protein of 25 kDa), selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type (WT) mice at the same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated.
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Binhui
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Zoulikha
authors.initials: Z
authors.lastname: Azzegagh
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Jaramillo
authors.affiliation: Cystic Fibrosis Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599, U.S.A.
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, U.S.A.
authors.forename: Ana
authors.initials: A
authors.lastname: Pardo-Saganta
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Rustam
authors.initials: R
authors.lastname: Bagirzadeh
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Flores
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Tang
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Jing
authors.initials: J
authors.lastname: Tu
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Alanis
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, U.S.A.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Evans
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Michele
authors.initials: M
authors.lastname: Guindani
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, U.S.A.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Roche
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, U.S.A.
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Rajagopal
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Jichao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Cystic Fibrosis Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599, U.S.A.
authors.forename: C William
authors.initials: CW
authors.lastname: Davis
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Tuvim
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A. bdickey@mdanderson.org.
authors.forename: Burton F
authors.initials: BF
authors.lastname: Dickey
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009077:Mucins / Q000378:metabolism*; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009077:Mucins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C107017:Snap23 protein, mouse
keywords: 23-kDa paralogue of synaptosome-associated protein of 25 kDa (SNAP23); exocytosis; mucin; mucus; secretion