Background Lysosomes digest extracellular material from the endocytic pathway and intracellular material from the autophagic pathway.This process is performed by the resident hydrolytic enzymes activated by the highly...Background Lysosomes digest extracellular material from the endocytic pathway and intracellular material from the autophagic pathway.This process is performed by the resident hydrolytic enzymes activated by the highly acidic pH within the lysosomal lumen.Lysosome pH gradients are mainly maintained by the vacuolar(H+)ATPase(or V-ATPase),which pumps protons into lysosomal lumen by consuming ATP.Dysfunction of V-ATPase affects lysosomal acidification,which disrupts the clearance of substrates and leads to many disorders,including neurodegenerative diseases.Main body As a large multi-subunit complex,the V-ATPase is composed of an integral membrane V0 domain involved in proton translocation and a peripheral V1 domain catalyzing ATP hydrolysis.The canonical functions of V-ATPase rely on its H+-pumping ability in multiple vesicle organelles to regulate endocytic traffic,protein processing and degradation,synaptic vesicle loading,and coupled transport.The other non-canonical effects of the V-ATPase that are not readily attributable to its proton-pumping activity include membrane fusion,pH sensing,amino-acid-induced activation of mTORC1,and scaffolding for protein-protein interaction.In response to various stimuli,V-ATPase complex can reversibly dissociate into V1 and V0 domains and thus close ATP-dependent proton transport.Dysregulation of pH and lysosomal dysfunction have been linked to many human diseases,including neurodegenerative disorders such as Alzheimer disease,Parkinson’s disease,amyotrophic lateral sclerosis as well as neurodegenerative lysosomal storage disorders.Conclusion V-ATPase complex is a universal proton pump and plays an important role in lysosome acidification in all types of cells.Since V-ATPase dysfunction contributes to the pathogenesis of multiple neurodegenerative diseases,further understanding the mechanisms that regulate the canonical and non-canonical functions of V-ATPase will reveal molecular details of disease process and help assess V-ATPase or molecules related to its regulation as th展开更多
A vacuolar ATPase (V-ATPase.) B subunit gene has been cloned and characterized front a phosphorus starvation induced rice root subtractive cDNA library by suppression subtractive hybridization (SSH) method and RT-PCR ...A vacuolar ATPase (V-ATPase.) B subunit gene has been cloned and characterized front a phosphorus starvation induced rice root subtractive cDNA library by suppression subtractive hybridization (SSH) method and RT-PCR amplification. This gene encodes a polypeptide of 487 amino acid residues, containing a conservative ATP binding site and with a molecular weight of 54.06 kD and an isoelectric point of 4.99, southern analysis of the. genomic DNA indicates that V-ATPase B subunit is encoded by a single gene in rice genome. The amino acid homologies of V-ATPase B subunits among different organisms range from 76% to 97% and reveals that the evolution of V-ATPase B subunit is accompanied with the biological evolution. Expression pattern analysis indicated that the maximal expression of V-ATPase B subunit gene occurred at an early stage (6 - 12 h) after phosphorus starvation in roots, and lately stage (24 - 48 It) in leaves. Under phosphorus deficiency, the up-regulated expression of V-ATPase gene was presumed to strengthen the proton transport and provide the required energy to maintain an electrochemical gradient across the tonoplast to facilitate Phosphorus transport.展开更多
The vacuolar (H+)-ATPases (V-ATPases) are ATP-driven proton pumps with multiple functions in many organisms. In this study, we performed structural and functional analysis of vha55 gene that encodes V-ATPase subunit B...The vacuolar (H+)-ATPases (V-ATPases) are ATP-driven proton pumps with multiple functions in many organisms. In this study, we performed structural and functional analysis of vha55 gene that encodes V-ATPase subunit B in the smokybrown cockroach Periplaneta fuliginosa (Blattodea). We observed a high homology score of the deduced amino acid sequences between 10 species in seven orders. RNAi of the vha55 gene in R fuliginosa caused nymphal/nymphal molting defects with incomplete shedding of old cuticles, growth inhibition, as well as bent and wrinkled cuticles of thoraxes and abdominal segments. Since growth inhibition caused by vha55 RNAi did not interfere in the commencement of cockroach molting, molting timing and body growth might be controlled by independent mechanism. Our study suggested V-ATPases might be a good candidate molecule for evolutionary and developmental studies of insect molting.展开更多
基金This work was supported in part by grants R01NS107505 and R01NS095269 to Z.M.
文摘Background Lysosomes digest extracellular material from the endocytic pathway and intracellular material from the autophagic pathway.This process is performed by the resident hydrolytic enzymes activated by the highly acidic pH within the lysosomal lumen.Lysosome pH gradients are mainly maintained by the vacuolar(H+)ATPase(or V-ATPase),which pumps protons into lysosomal lumen by consuming ATP.Dysfunction of V-ATPase affects lysosomal acidification,which disrupts the clearance of substrates and leads to many disorders,including neurodegenerative diseases.Main body As a large multi-subunit complex,the V-ATPase is composed of an integral membrane V0 domain involved in proton translocation and a peripheral V1 domain catalyzing ATP hydrolysis.The canonical functions of V-ATPase rely on its H+-pumping ability in multiple vesicle organelles to regulate endocytic traffic,protein processing and degradation,synaptic vesicle loading,and coupled transport.The other non-canonical effects of the V-ATPase that are not readily attributable to its proton-pumping activity include membrane fusion,pH sensing,amino-acid-induced activation of mTORC1,and scaffolding for protein-protein interaction.In response to various stimuli,V-ATPase complex can reversibly dissociate into V1 and V0 domains and thus close ATP-dependent proton transport.Dysregulation of pH and lysosomal dysfunction have been linked to many human diseases,including neurodegenerative disorders such as Alzheimer disease,Parkinson’s disease,amyotrophic lateral sclerosis as well as neurodegenerative lysosomal storage disorders.Conclusion V-ATPase complex is a universal proton pump and plays an important role in lysosome acidification in all types of cells.Since V-ATPase dysfunction contributes to the pathogenesis of multiple neurodegenerative diseases,further understanding the mechanisms that regulate the canonical and non-canonical functions of V-ATPase will reveal molecular details of disease process and help assess V-ATPase or molecules related to its regulation as th
文摘A vacuolar ATPase (V-ATPase.) B subunit gene has been cloned and characterized front a phosphorus starvation induced rice root subtractive cDNA library by suppression subtractive hybridization (SSH) method and RT-PCR amplification. This gene encodes a polypeptide of 487 amino acid residues, containing a conservative ATP binding site and with a molecular weight of 54.06 kD and an isoelectric point of 4.99, southern analysis of the. genomic DNA indicates that V-ATPase B subunit is encoded by a single gene in rice genome. The amino acid homologies of V-ATPase B subunits among different organisms range from 76% to 97% and reveals that the evolution of V-ATPase B subunit is accompanied with the biological evolution. Expression pattern analysis indicated that the maximal expression of V-ATPase B subunit gene occurred at an early stage (6 - 12 h) after phosphorus starvation in roots, and lately stage (24 - 48 It) in leaves. Under phosphorus deficiency, the up-regulated expression of V-ATPase gene was presumed to strengthen the proton transport and provide the required energy to maintain an electrochemical gradient across the tonoplast to facilitate Phosphorus transport.
文摘The vacuolar (H+)-ATPases (V-ATPases) are ATP-driven proton pumps with multiple functions in many organisms. In this study, we performed structural and functional analysis of vha55 gene that encodes V-ATPase subunit B in the smokybrown cockroach Periplaneta fuliginosa (Blattodea). We observed a high homology score of the deduced amino acid sequences between 10 species in seven orders. RNAi of the vha55 gene in R fuliginosa caused nymphal/nymphal molting defects with incomplete shedding of old cuticles, growth inhibition, as well as bent and wrinkled cuticles of thoraxes and abdominal segments. Since growth inhibition caused by vha55 RNAi did not interfere in the commencement of cockroach molting, molting timing and body growth might be controlled by independent mechanism. Our study suggested V-ATPases might be a good candidate molecule for evolutionary and developmental studies of insect molting.
