GOLAC: An Endogenous Anion Channel of the Golgi Complex

Nordeen, Mark H.; Jones, Steven M.; Howell, Kathryn E.; Caldwell, John H.

doi:10.1016/s0006-3495(00)76832-9

Cited by 37 publications

(30 citation statements)

References 50 publications

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“…In this circumstance, it is likely that eliminating CFTR has no effect on pH G , because other K ϩ and Cl Ϫ channels can provide sufficient counterion conductance to ensure that membrane potential in the Golgi is small and therefore has little effect on H ϩ pumps or leaks. Two other studies have provided evidence for the presence of Cl Ϫ channels in the Golgi: Nordeen et al (35) found an anion channel in enriched Golgi fractions, and Schwappach et al (46) found that Gef1p (the only yeast ClC Cl Ϫ channel) localizes to the Golgi. Additionally, elimination of Gef1p from yeast does result in altered cation homeostasis (17) but does not effect Kar2p secretion or glycosylation of invertase, both dependent on an acidic Golgi (46).…”

Section: Cftr Counterion Conductance and Membrane Potential In Detementioning

confidence: 99%

Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells

Chandy¹,

Grabe

Moore³

et al. 2001

American Journal of Physiology-Cell Physiology

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Work addressing whether cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in regulating organelle pH has remained inconclusive. We engineered a pH-sensitive excitation ratiometric green fluorescent protein (pHERP) and targeted it to the Golgi with sialyltransferase (ST). As determined by ratiometric imaging of cells expressing ST-pHERP, Golgi pH (pHG) of HeLa cells was 6.4, while pHG of mutant (ΔF508) and wild-type CFTR-expressing (WT-CFTR) respiratory epithelia were 6.7–7.0. Comparison of genetically matched ΔF508 and WT-CFTR cells showed that the absence of CFTR statistically increased Golgi acidity by 0.2 pH units, though this small difference was unlikely to be physiologically important. Golgi pH was maintained by a H+ vacuolar (V)-ATPase countered by a H+leak, which was unaffected by CFTR. To estimate Golgi proton permeability ( P H+ ), we modeled transient changes in pHG induced by inhibiting the V-ATPase and by acidifying the cytosol. This analysis required knowing Golgi buffer capacity, which was pH dependent. Our in vivo estimate is that Golgi P H+ = 7.5 × 10−4 cm/s when pHG = 6.5, and surprisingly, P H+ decreased as pHG decreased.

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Section: Cftr Counterion Conductance and Membrane Potential In Detementioning

confidence: 99%

Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells

Chandy¹,

Grabe

Moore³

et al. 2001

American Journal of Physiology-Cell Physiology

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“…Eukaryotic cells contain functional channels in the endoplasmic reticulum and sarcoplasmic reticulum [1][2][3] ; specific ion channels have also been identified in the inner nuclear membrane [4], mitochondrial membranes [5,6], Golgi membranes [7,8] and secretory vesicles [9][10][11]. Some of these channels are involved in the mobilization of intracellular Ca# + [1,2] and the transport of metabolites [5].…”

Section: Introductionmentioning

confidence: 99%

Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms

Suginta

Karoulias

Aitken

et al. 2001

Biochemical Journal

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Mammalian chloride intracellular channel (CLIC) (p64-related) proteins are widely expressed, with an unusual dual localization as both soluble and integral membrane proteins. The molecular basis for their cellular localization and ion channel activity remains unclear. To help in addressing these problems, we identified novel rat brain CLIC4 (p64H1) binding partners by affinity chromatography, mass spectrometric analysis and microsequencing. Brain CLIC4 binds dynamin I, α-tubulin, β-actin, creatine kinase and two 14-3-3 isoforms ; the interactions are confirmed in i o by immunoprecipitation. Gel overlay and reverse pull-down assays indicate that the binding of CLIC4 to dynamin I and 14-3-3ζ is direct. In HEK-293 cells, biochemical and immunofluorescence analyses show partial co-localization of

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“…However, for many Cl Ϫ channels, it has not been possible to associate molecular identity with function (19). In hepatocytes, as yet unidentified Cl Ϫ channels participate in cell volume regulation (1,7,22,23) and acidification of intracellular organelles (5,24,28,36). The ClC Cl Ϫ channel family has proven to be important in diverse cellular functions (10,14,40).…”

mentioning

confidence: 99%

The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells

Li¹,

Wang²,

Zhao³

et al. 2002

American Journal of Physiology-Cell Physiology

124

127

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ClC-3 is a voltage-gated Cl−channel that is highly conserved and widely expressed, although its function, localization, and properties remain a matter of considerable debate. In this study, we have shown that heterologous expression of ClC-3 in either Chinese hamster ovary (CHO-K1) or human hepatoma (Huh-7) cells results in the formation of large, acidic vesicular structures within cells. Vesicle formation is prevented by bafilomycin, an inhibitor of the vacuolar ATPase, and is not induced by an E224A mutant of ClC-3 with altered channel activity. This demonstrates that vesicle formation requires both proton pumping and Cl−channel activity. Manipulation of the intracellular Cl−concentration demonstrated that the ClC-3-associated vesicles shrink and swell consistent with a highly Cl−-permeable membrane. The ClC-3 vesicles were identified as lysosomes based on their colocalization with the lysosome-associated proteins lamp-1, lamp-2, and cathepsin D and on their failure to colocalize with fluorescently labeled endosomes. We conclude that ClC-3 is an intracellular channel that conducts Cl− when it is present in intracellular vesicles. Its overexpression results in its appearance in enlarged lysosome-like structures where it contributes to acidification by charge neutralization.

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GOLAC: An Endogenous Anion Channel of the Golgi Complex

Cited by 37 publications

References 50 publications

Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells

Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells

Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms

The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells

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