The role of bestrophin in airway epithelial ion transport

Duta, V.; Szkotak, Artur; Nahirney, Drew; Duszyk, Marek

doi:10.1016/j.febslet.2004.10.068

Cited by 29 publications

(26 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data suggest that the basolateral current in airway epithelia does not match the characteristics of previously described channels. Previous studies in Calu-3 cells suggested that the Cl Ϫ channel bestrophin-1 may be responsible for the majority of basolateral Cl Ϫ conductance (10). Reducing expression of bestrophin-1 decreased the effect of basolateral DIDS on Cl Ϫ concentration gradient, similar to experiment in Fig.…”

Section: What Is the Identity Of The Basolateral CLsupporting

confidence: 86%

“…In airway epithelia, intracellular Ca 2ϩ has been reported to activate basolateral K ϩ channels (25), some apical non-CFTR Cl Ϫ channels (2), and basolateral Cl Ϫ channels (10,37). To test whether the basolateral Cl Ϫ conductance was similarly regulated, we treated cells with the Ca 2ϩ ionophore ionomycin.…”

Section: Regulation Of Basolateral CL ϫ Conductance To Further Undermentioning

confidence: 99%

See 1 more Smart Citation

Basolateral chloride current in human airway epithelia

Itani¹,

Lamb²,

Melvin³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Electrolyte transport by airway epithelia regulates the quantity and composition of liquid covering the airways. Previous data indicate that airway epithelia can absorb NaCl. At the apical membrane, cystic fibrosis transmembrane conductance regulator (CFTR) provides a pathway for Cl− absorption. However, the pathways for basolateral Cl− exit are not well understood. Earlier studies, predominantly in cell lines, have reported that the basolateral membrane contains a Cl− conductance. However, the properties have varied substantially in different epithelia. To better understand the basolateral Cl− conductance in airway epithelia, we studied primary cultures of well-differentiated human airway epithelia. The basolateral membrane contained a Cl− current that was inhibited by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS). The current-voltage relationship was nearly linear, and the halide selectivity was Cl− > Br− >> I−. Several signaling pathways increased the current, including elevation of cellular levels of cAMP, activation of protein kinase C (PKC), and reduction of pH. In contrast, increasing cell Ca2+ and inducing cell swelling had no effect. The basolateral Cl− current was present in both cystic fibrosis (CF) and non-CF airway epithelia. Likewise, airway epithelia from wild-type mice and mice with disrupted genes for ClC-2 or ClC-3 all showed similar Cl− currents. These data suggest that the basolateral membrane of airway epithelia possesses a Cl− conductance that is not due to CFTR, ClC-2, or ClC-3. Its regulation by cAMP and PKC signaling pathways suggests that coordinated regulation of Cl− conductance in both apical and basolateral membranes may be important in controlling transepithelial Cl− movement.

show abstract

Section: What Is the Identity Of The Basolateral CLsupporting

confidence: 86%

Section: Regulation Of Basolateral CL ϫ Conductance To Further Undermentioning

confidence: 99%

Basolateral chloride current in human airway epithelia

Itani¹,

Lamb²,

Melvin³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…However, expressed mouse Tmem16A was markedly more sensitive to a panel of anion channel blockers than the CaCC found in native secretory cells, and importantly, knockdown of Tmem16A produced only a modest effect (ϳ25% inhibition) on saliva secretion (6) raising the possibility that another CaCC is present in salivary gland acinar cells. Similarly, small interfering RNA to Best1 suppressed endogenous Ca 2ϩ -activated Cl Ϫ currents in airway and colonic epithelial cells (1,24), whereas expression of Best1 transcripts and CaCC activity were up-regulated in neurons following injury (7), implying that Best1 encodes a Ca 2ϩ -activated Cl Ϫ channel in these various cell types. Nevertheless, the Ca 2ϩ -activated Cl Ϫ current in the retinal pigment epithelium of Best1 null mice is normal (25).…”

mentioning

confidence: 99%

Tmem16A Encodes the Ca2+-activated Cl− Channel in Mouse Submandibular Salivary Gland Acinar Cells

Romanenko

Catalán

Brown

et al. 2010

Journal of Biological Chemistry

182

199

View full text Add to dashboard Cite

show abstract

“…BEST1 expression was initially found at the high level in the RPE with lower levels in the testis and brain (47); subsequently, it has also been found in specific cell types, such as airway epithelial cells (48) and hippocampal astrocytes (49). BEST1 encodes bestrophin-1, a multispan transmembrane protein that seems to function as both a Ca 2ϩ -activated chloride channel (50,51) and a regulator of a voltage-gated Ca 2ϩ channel (52)(53)(54).…”

mentioning

confidence: 99%

SOX9, through Interaction with Microphthalmia-associated Transcription Factor (MITF) and OTX2, Regulates BEST1 Expression in the Retinal Pigment Epithelium

Masuda

Esumi

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

BEST1 is highly and preferentially expressed in the retinal pigment epithelium (RPE) and causes Best macular dystrophy when mutated. We previously demonstrated that the human BEST1 upstream region ؊154 to ؉38 bp is sufficient to direct expression in the RPE of transgenic mice, and microphthalmiaassociated transcription factor (MITF) and OTX2 regulate this BEST1 promoter. However, a number of questions remained. Here, we show that yeast one-hybrid screen with bait corresponding to BEST1 ؊120 to ؊88 bp identified the SOX-E factors, SOX8, SOX9, and SOX10. A paired SOX site was found in this bait, and mutation of either of the paired sites significantly decreased BEST1 promoter activity in RPE primary cultures. Among the SOX-E genes, SOX9 is highly and preferentially expressed in the RPE, and chromatin immunoprecipitation with fresh RPE cells revealed binding of SOX9, but not SOX10, to the BEST1 region where the paired SOX site is located. BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. Importantly, SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles. A combination of the expression patterns of SOX9, MITF, and OTX2 yielded tissue distribution remarkably similar to that of BEST1. Lastly, the BEST1 promoter was also active in Sertoli cells of the testis in transgenic mice where SOX9 is highly expressed. These results define SOX9 as a key regulator of BEST1 expression and demonstrate for the first time its functional role in the RPE. The retinal pigment epithelium (RPE)2 has many specialized functions essential for vision and is indispensable for the survival and function of retinal photoreceptors (1, 2). RPE cells and melanocytes, two major pigmented cells in the body, share pigment-related genes such as tyrosinase (Tyr) and dopachrome tautomerase (Dct) and transcription factors regulating them such as microphthalmia-associated transcription factor (MITF); otherwise, these two cell types are distinct in many aspects. Although the molecular networks controlling gene expression in melanocytes have been extensively studied (3, 4), those in the RPE are still poorly understood. Among the key transcription factors required for RPE specification and development are MITF (3-9) and orthodenticle homeobox 2 (OTX2) (10 -14). MITF and OTX2 proteins physically interact with each other and cooperatively activate some pigment-related genes in the RPE, such as QNR71 and Tyr (15). Our previous studies found that human BEST1, a gene that is highly and preferentially expressed in the RPE but not related to pigment, is also regulated by . However, a number of questions remained to be answered. Recently, it has been found unintentionally that SRY (sex-determining region Y) box 9 (SOX9) is robustly expressed in mouse RPE throughout embryonic development and into postnatal stages (19).SOX9 is a member of the SOX family of transcription factors, which is characterized by the hig...

show abstract

The role of bestrophin in airway epithelial ion transport

Cited by 29 publications

References 33 publications

Basolateral chloride current in human airway epithelia

Basolateral chloride current in human airway epithelia

Tmem16A Encodes the Ca2+-activated Cl− Channel in Mouse Submandibular Salivary Gland Acinar Cells

SOX9, through Interaction with Microphthalmia-associated Transcription Factor (MITF) and OTX2, Regulates BEST1 Expression in the Retinal Pigment Epithelium

Contact Info

Product

Resources

About