Ins(3,4,5,6)P sub4 inhibits an apical calcium-activated chloride conductance in polarized monolayers of a cystic fibrosis cell-line

Carew, Mark; Yang, Xiao; Schultz, Carsten; Shears, Stephen B.

doi:10.1074/jbc.m002316200

Cited by 29 publications

(48 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Total PLC activity in WT and CF MTEs is shown in Fig. 3; these data were obtained by summation of levels of Ins(1,4,5)P 3 and all of its downstream metabolites (see Carew et al, 2000). A bi-phasic stimulation of PLC was observed (Fig.…”

Section: Journal Of Cell Science 119 (7)mentioning

confidence: 99%

“…Note that Ins(1,4,5,6)P 4 , a constituent of many cells, co-elutes with Ins(3,4,5,6)P 4 upon HPLC (because the two polyphosphates are enantiomers). Stereospecific, enzymatic analysis of the Ins(3,4,5,6)P 4 peak (Carew et al, 2000) revealed (data not shown) that it contained <5% Ins(1,4,5,6)P 4 .…”

Section: Journal Of Cell Science 119 (7)mentioning

confidence: 99%

“…We specifically elevated intracellular levels of Ins(3,4,5,6)P 4 by treating the monolayer culture with a cell-permeable, bio-activatable analogue of this inositol phosphate (Vajanaphanich et al, 1994;Rudolf et al, 2003). This type of experiment has previously only been performed in two cell lines, in T 84 colonic epithelia and CFPAC-1 pancreatic epithelia (Vajanaphanich et al, 1994;Carew et al, 2000). We were able to show that 50 M Bt 2 Ins(3,4,5,6)P 4 /PM (the analogue of Ins(3,4,5,6)P 4 ) inhibited ⌬I SC by 40-50% in both CF and WT MTEs (Fig.…”

Section: Insmentioning

confidence: 99%

“…However, we have hypothesized that the efficacy of this drug is constrained by the actions of one particular inositol phosphate, inositol (3,4,5,6)-tetrakisphosphate [Ins(3,4,5,6)P 4 ] . Ins(3,4,5,6)P 4 accumulates following the activation of PLC (Menniti et al, 1990;Carew et al, 2000) and has been shown to inhibit certain CaCCs (Ismailov et al, 1996;Xie et al, 1996;Carew et al, 2000;Ho et al, 2001). On the other hand, not all CaCCs are regulated by Ins(3,4,5,6)P 4 (Sasakawa et al, 1994; nor has it previously been demonstrated that airway epithelia use Ins(3,4,5,6)P 4 to regulate Cl -secretion.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Yang

Reece

Gabriel

et al. 2006

Journal of Cell Science

View full text Add to dashboard Cite

A new aspect of research into the pathogenesis of cystic fibrosis (CF) is a genetics-based search for `modifier genes' that may affect the severity of CF lung disease. Using an alternative, cell biological approach, we show that ITPK1 should be considered a modifier gene. ITPK1 synthesizes an intracellular signal, inositol (3,4,5,6)-tetrakisphosphate [Ins(3,4,5,6)P4]. A bio-activatable, cell-permeable analogue of Ins(3,4,5,6)P4 inhibited Ca2+-dependent secretion of Cl- from polarized monolayers of immortalized mouse tracheal epithelial cells (MTEs). Analysis by high-pressure liquid chromatography showed endogenous Ins(3,4,5,6)P4 levels in CF MTEs were approximately 60% below those in wild-type MTEs (P<0.03). This adaptation, which improves purinergic activation of Ca2+-dependent Cl- secretion in CF MTEs, was exceptionally specific; there was no effect upon the cellular levels of all the other inositol phosphate signals. Real-time PCR provided the explanation: the level of ITPK1 expression in wild-type MTEs was twice as high as that in CF MTEs (P<0.002). The biological impact of this differential gene expression is amplified by ITPK1 being concentrated at the apical membrane of MTEs, which we discovered following confocal immunofluorescence microscopy. Compartmentalization of Ins(3,4,5,6)P4 synthesis adjacent to its site of action will enhance its regulatory capacity.

show abstract

Section: Journal Of Cell Science 119 (7)mentioning

confidence: 99%

Section: Journal Of Cell Science 119 (7)mentioning

confidence: 99%

Section: Insmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Yang

Reece

Gabriel

et al. 2006

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Inositol 3,4,5,6-tetra kis phosphate [Ins(3,4,5,6)P 4 ] has been demonstrated to negatively regulate Ca 2 ϩ -activated Cl Ϫ channels (Vajanaphanich et al, 1994;Ismailov et al, 1996;Xie et al, 1996Xie et al, , 1998Barrett et al, 1998;Nilius et al, 1998;Yang et al, 1999;Carew et al, 2000;Ho et al, 2000Ho et al, , 2001. During a screen of a number of different inositol polyphosphates for effects on pollen tube growth, Ins(3,4,5,6)P 4 was identified as a strong effector (L. Zonia, unpublished data).…”

Section: Introductionmentioning

confidence: 99%

Oscillatory Chloride Efflux at the Pollen Tube Apex Has a Role in Growth and Cell Volume Regulation and Is Targeted by Inositol 3,4,5,6-Tetrakisphosphate

et al. 2002

View full text Add to dashboard Cite

New Insights on the Regulation of Ca²⁺‐Activated Chloride Channel TMEM16A

Wang

et al. 2016

Journal Cellular Physiology

View full text Add to dashboard Cite

TMEM16A, also known as anoctamin 1, is a recently identified Ca -activated chloride channel and the first member of a 10-member TMEM16 family. TMEM16A dysfunction is implicated in many diseases such as cancer, hypertension, and cystic fibrosis. TMEM16A channels are well known to be dually regulated by voltage and Ca . In addition, recent studies have revealed that TMEM16A channels are regulated by many molecules such as calmodulin, protons, cholesterol, and phosphoinositides, and a diverse range of stimuli such as thermal and mechanical stimuli. A better understanding of the regulatory mechanisms of TMEM16A is important to understand its physiological and pathological role. Recently, the crystal structure of a TMEM16 family member from the fungus Nectria haematococcaten (nhTMEM16) is discovered, and provides valuable information for studying the structure and function of TMEM16A. In this review, we discuss the structure and function of TMEM16A channels based on the crystal structure of nhTMEM16A and focus on the regulatory mechanisms of TMEM16A channels. J. Cell. Physiol. 232: 707-716, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

Ins(3,4,5,6)P sub4 inhibits an apical calcium-activated chloride conductance in polarized monolayers of a cystic fibrosis cell-line

Cited by 29 publications

References 49 publications

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Oscillatory Chloride Efflux at the Pollen Tube Apex Has a Role in Growth and Cell Volume Regulation and Is Targeted by Inositol 3,4,5,6-Tetrakisphosphate

New Insights on the Regulation of Ca²⁺‐Activated Chloride Channel TMEM16A

Contact Info

Product

Resources

About

Ins(3,4,5,6)P sub4 inhibits an apical calcium-activated chloride conductance in polarized monolayers of a cystic fibrosis cell-line

Cited by 29 publications

References 49 publications

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

Oscillatory Chloride Efflux at the Pollen Tube Apex Has a Role in Growth and Cell Volume Regulation and Is Targeted by Inositol 3,4,5,6-Tetrakisphosphate

New Insights on the Regulation of Ca2+‐Activated Chloride Channel TMEM16A

Contact Info

Product

Resources

About

New Insights on the Regulation of Ca²⁺‐Activated Chloride Channel TMEM16A