Chloride channels of intracellular organelles

Al‐Awqati, Qais

doi:10.1016/0955-0674(95)80006-9

Cited by 99 publications

(90 citation statements)

References 49 publications

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“…Bars, 200 nm. ATPases and ion exchangers [Glickman et al, 1983;Al Awqati, 1995;Demareux et al, 1998;Thompson et al, 2002;Nakamura et al, 2005]. Therefore, we examined whether the actin toxin-induced alterations of Golgi cisternae ultrastructure were accompanied by changes in intra-Golgi pH (pH G ).…”

Section: Depolymerization But Not Stabilization Of F-actin Raises Intmentioning

confidence: 99%

Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra‐Golgi pH

Lázaro‐Diéguez

Jiménez

Barth

et al. 2006

Cell Motil. Cytoskeleton

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Here we examine the contribution of actin dynamics to the architecture and pH of the Golgi complex. To this end, we have used toxins that depolymerize (cytochalasin D, latrunculin B, mycalolide B, and Clostridium botulinum C2 toxin) or stabilize (jasplakinolide) filamentous actin. When various clonal cell lines were examined by epifluorescence microscopy, all of these actin toxins induced compaction of the Golgi complex. However, ultrastructural analysis by transmission electron microscopy and electron tomography/three-dimensional modelling of the Golgi complex showed that F-actin depolymerization first induces perforation/fragmentation and severe swelling of Golgi cisternae, which leads to a completely disorganized structure. In contrast, F-actin stabilization results only in cisternae perforation/fragmentation. Concomitantly to actin depolymerization-induced cisternae swelling and disorganization, the intra-Golgi pH significantly increased. Similar ultrastructural and Golgi pH alkalinization were observed in cells treated with the vacuolar H þ -ATPases inhibitors bafilomycin A1 and concanamycin A. Overall, these results suggest that actin filaments are implicated in the preservation of the flattened shape of Golgi cisternae. This maintenance seems to be mediated by the regulation of the state of F-actin assembly on the Golgi pH homeostasis. Cell Motil. Cytoskeleton 63: 778-791, 2006. '

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Section: Depolymerization But Not Stabilization Of F-actin Raises Intmentioning

confidence: 99%

Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra‐Golgi pH

Lázaro‐Diéguez

Jiménez

Barth

et al. 2006

Cell Motil. Cytoskeleton

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“…However, the molecular identities and cellular roles of many intracellular channels remain to be discovered. These include the ' charge-compensating ' anion channels found in some acidic vesicles containing proton pumps [12]. In addition, just as plasma membrane ion channels help to regulate cell volume [13,14], intracellular ion channels might regulate the volume of intracellular organelles or might store channels for rapid on-demand incorporation into, and removal from, the plasma membrane [14].…”

Section: Introductionmentioning

confidence: 99%

“…The bovine renal protein p64 [12] was the first member of a new family of putative intracellular anion channel proteins, many of which are now collectively called chloride intracellular channel (CLIC) proteins, to be identified at the molecular level [15]. CLIC4, originally named p64H1 because it was the first homologue of p64 to be discovered [16], is a 28.6 kDa protein corresponding to a cDNA cloned from rat brain.…”

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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“…The decrease in pH necessary to dissolve the inorganic phase is mediated by an active transport of protons over the ruffled border membrane, which is driven by an osteoclastic Vtype H ϩ ATPase. 7,8 At the same time a passive transport of chloride through chloride channels preserves the electroneutrality, 9 and is mediated by the chloride channel ClC-7. 10,11 Degradation of the organic phase of bone is for the major part mediated by the enzyme cathepsin K, which degrades collagen type I.…”

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confidence: 99%

Acidification of the Osteoclastic Resorption Compartment Provides Insight into the Coupling of Bone Formation to Bone Resorption

Karsdal

Henriksen

Sørensen

et al. 2005

The American Journal of Pathology

139

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Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibition of bone resorption without inhibition of bone formation. We investigated the role of acidification in human osteoclastic resorption and life span in vitro using inhibitors of chloride channels (NS5818/ NS3696), the proton pump (bafilomycin) and cathepsin K. We found that bafilomycin and NS5818 dose dependently inhibited acidification of the osteoclastic resorption compartment and bone resorption. Inhibition of bone resorption by inhibition of acidification, but not cathepsin K inhibition, augmented osteoclast survival, which resulted in a 150 to 300% increase in osteoclasts compared to controls. We investigated the effect of inhibition of osteoclastic acidification in vivo by using the rat ovariectomy model with twice daily oral dosing of NS3696 at 50 mg/kg for 6 weeks. We observed a 60% decrease in resorption (DPYR), increased tartrate-resistant acid phosphatase levels, and no effect on bone formation evaluated by osteocalcin. We speculate that attenuated acidification inhibits dissolution of the inorganic phase of bone and results in an increased number of nonresorbing osteoclasts that are responsible for the coupling to normal bone formation. Thus, we suggest that acidification is essential for normal bone remodeling and that attenuated acidification leads to uncoupling with decreased bone resorption and unaffected bone formation. The coupling process is understood as a bone formation response that is the consequence of bone resorption, with an amount of bone formed that is equal to that resorbed. 1,2 Uncoupling occurs when the balance between formation and resorption is disturbed, which might lead to either osteopetrosis or osteoporosis. 3,4 Although it has long been appreciated that bone formation is tightly coupled to bone resorption in normal adult bone turnover, 5,6 this coupling can be dissociated in some circumstances, for example during skeletal growth and in some but not all osteopetrotic mutations.Bone consists of two phases, the organic phase, which contains proteins such as collagen type I, and the inorganic phase, which consists of crystallized calcium phosphate. Dissolution of the inorganic phase of bone under the osteoclast attached to the bone surface is a prerequisite for degradation of the organic phase, and is mediated by acidification of the resorption compartment. The decrease in pH necessary to dissolve the inorganic phase is mediated by an active transport of protons over the ruffled border membrane, which is driven by an osteoclastic Vtype H ϩ ATPase. 7,8 At the same time a passive transport of chloride through chloride channels preserves the electroneutrality, 9 and is mediated by the chloride channel ClC-7. 10,11 Degradation of the organic phase of bone is for the major part mediated b...

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Chloride channels of intracellular organelles

Cited by 99 publications

References 49 publications

Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra‐Golgi pH

Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra‐Golgi pH

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

Acidification of the Osteoclastic Resorption Compartment Provides Insight into the Coupling of Bone Formation to Bone Resorption

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