nPKCε, a P2Y2-R downstream effector in regulated mucin secretion from airway goblet cells

Camille Ehre, Yunxiang Zhu, Lubna H. Abdullah, John Olsen, Keiichi I. Nakayama, Keiko Nakayama, Robert O. Messing, C. William Davis

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Airway goblet cell mucin secretion is controlled by agonist activation of P2Y2 purinoceptors, acting through Gq/PLC, inositol-1,4,5- trisphosphate (IP3), diacylglycerol, Ca2+ and protein kinase C (PKC). Previously, we showed that SPOC1 cells express cPKCα, nPKCβ, nPKCε, and nPKCη; of these, only nPKCδ translocated to the membrane in correlation with mucin secretion (Abdullah LH, Bundy JT, Ehre C, Davis CW. Am J Physiol Lung Physiol 285: L149-L160, 2003). We have verified these results and pursued the identity of the PKC effector isoform by testing the effects of altered PKC expression on regulated mucin release using SPOC1 cell and mouse models. SPOC1 cells overexpressing cPKCα, nPKCδ, and nPKCη had the same levels of ATPγS- and phorbol-1,2-myristate-13- acetate (PMA)-stimulated mucin secretion as the levels in empty retroviral vector expressing cells. Secretagogue-induced mucin secretion was elevated only in cells overexpressing nPKC (14.6 and 23.5%, for ATPγS and PMA). Similarly, only SPOC1 cells infected with a kinase-deficient nPKCε exhibited the expected diminution of stimulated mucin secretion, relative to wild-type (WT) isoform overexpression. ATPγS-stimulated mucin secretion from isolated, perfused mouse tracheas was diminished in P2Y2-R null mice by 82% relative to WT mice, demonstrating the utility of mouse models in studies of regulated mucin secretion. Littermate WT and nPKCδ knockout (KO) mice had nearly identical levels of stimulated mucin secretion, whereas mucin release was nearly abolished in nPKCε KO mice relative to its WT littermates. We conclude that nPKCε is the effector isoform downstream of P2Y2-R activation in the goblet cell secretory response. The translocation of nPKCδ observed in activated cells is likely not related to mucin secretion but to some other aspect of goblet cell biology.

Original languageEnglish
Pages (from-to)C1445-C1454
JournalAmerican Journal of Physiology - Cell Physiology
Volume293
Issue number5
DOIs
Publication statusPublished - Nov 2007

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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