Functional coupling of V-ATPase and CLC-5

Dent’s disease is an X-linked renal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria and progressive renal failure. Disease aetiology is associated with mutations in the CLCN5 gene coding for the electrogenic 2Cl-/H＋ antiporter chloride channel 5 （CLC-5）, which is expressed in the apical endosomes of renal proximal tubules with the vacuolar type H＋-ATPase （V-ATPase）. Initially identified as a member of the CLC family of Cl- channels, CLC-5 was presumed to provide Cl shunt into the endosomal lumen to dissipate H＋ accumulation by V-ATPase, thereby facilitating efficient endosomal acidification. However, recent findings showing that CLC-5 is in fact not a Cl- channel but a 2Cl-/H＋ antiporter challenged this classical shunt model, leading to a renewed and intense debate on its physiological roles. Cl- accumulation via CLC-5 is predicted to play a critical role in endocytosis, as illustrated in mice carrying an artifcial Cl- channel mutation E211A that developed defective endocytosis but normal endo-somal acidification. Conversely, a recent functional analysis of a newly identifed disease-causing Cl- channel mutation E211Q in a patient with typical Dent’s disease confrmed the functional coupling between V-ATPase and CLC-5 in endosomal acidifcation, lending support to the classical shunt model. In this editorial, we will address the current recognition of the physiological role of CLC-5 with a specific focus on the functional coupling of V-ATPase and CLC-5.

Efects of sulfuric,nitric,and mixed acid rain on the decomposition of fne root litter in Southern China

Background:China has been increasingly subject to signifcant acid rain,which has negative impacts on forest ecosystems.Recently,the concentrations of NO_(3)^(−)in acid rain have increased in conjunction with the rapid rise of nitrogen deposition,which makes it difcult to precisely quantify the impacts of acid rain on forest ecosystems.Methods:For this study,mesocosm experiments employed a random block design,comprised of ten treatments involving 120 discrete plots(0.6 m×2.0 m).The decomposition of fne roots and dynamics of nutrient loss were evaluated under the stress of three acid rain analogues(e.g.,sulfuric(SO_(4)^(2−)/NO_(3)^(−)5:1),nitric(1:5),and mixed(1:1)).Furthermore,the infuences of soil properties(e.g.,soil pH,soil total carbon,nitrogen,C/N ratio,available phosphorus,available potassium,and enzyme activity)on the decomposition of fne roots were analyzed.Results:The soil pH and decomposition rate of fne root litter decreased when exposed to simulated acid rain with lower pH levels and higher NO_(3)^(−)concentrations.The activities of soil enzymes were signifcantly reduced when subjected to acid rain with higher acidity.The activities of soil urease were more sensitive to the efects of the SO_(4)^(2−)/NO_(3)^(−)(S/N)ratio of acid rain than other soil enzyme activities over four decomposition time periods.Furthermore,the acid rain pH signifcantly infuenced the total carbon(TC)of fne roots during decomposition.However,the S/N ratio of acid rain had signifcant impacts on the total nitrogen(TN).In addition,the pH and S/N ratio of the acid rain had greater impacts on the metal elements(K,Ca,and Al)of fne roots than did TC,TN,and total phosphorus.Structural equation modeling results revealed that the acid rain pH had a stronger indirect impact(0.757)on the decomposition rate of fne roots(via altered soil pH and enzyme activities)than direct efects.However,the indirect efects of the acid rain S/N ratio(0.265)on the fne root decomposition rate through changes in soil urease activities and the content of litter elements were lower than the pH of acid rain.Conclusions:Our results suggested that the acid rain S/N ratio exacerbates the inhibitory efects of acid rain pH on the decomposition of fne root litter.