BACKGROUND The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases(V-ATPase)is located on chromosome Xq28.Defects in certain subunits or accessory subunits of the V-ATPase...BACKGROUND The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases(V-ATPase)is located on chromosome Xq28.Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation(CDG).CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs.Therefore,the clinical presentation of patients with ATP6AP1-CDG varies widely.In this report,we present a case of ATP6AP1-CDG in a Chinese infant,with clinical features and genotype.CASE SUMMARY An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital.A post-admission examination at our hospital revealed abnormalities in the infant’s liver,brain,and immune system.Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A(p.E346K)in exon 9 of the ATP6AP1 gene.This variant of the ATP6AP1 gene has not been reported in East Asian countries until now.CONCLUSION Based on the infant’s clinical manifestations and the results of genetic detection,he was clearly diagnosed with ATP6AP1-CDG.The clinical manifestations of children with CDG vary widely.Genetic testing analysis helps in the clinical diagnosis of children with CDG.展开更多
Sulfur nutrition is crucial for plant growth and development,as well as crop yield and quality.Inorganic sulfate in the soil is the major sulfur source for plants.After uptake,sulfate is activated by ATP sulfurylase,a...Sulfur nutrition is crucial for plant growth and development,as well as crop yield and quality.Inorganic sulfate in the soil is the major sulfur source for plants.After uptake,sulfate is activated by ATP sulfurylase,and then gets assimilated into sulfur-containing metabolites.However,the mechanism of regulation of sulfate levels by ATP sulfurylase is unclear.Here,we investigated the control of sulfate levels by miR395-mediated regulation of APS1/3/4.Sulfate was over-accumulated in the shoots of miR395 over-expression plants in which the expression of the APS1,APS3,and APS4 genes was suppressed.Accordingly,reduced expression of miR395 caused a decline of sulfate concentration.In agreement with these results,over-expression of the APS1,APS3,and APS4 genes led to the reduction of sulfate levels.Differential expression of these three APS genes in response to sulfate starvation implied that they have different functions.Further investigation revealed that the regulation of sulfate levels mediated by miR395 depends on the repression of its APS targets.Unlike the APS1,APS3,and APS4 genes,which encode plastid-localized ATP sulfurylases,the APS2 gene encodes a cytosolic version of ATP sulfurylase.Genetic analysis indicated that APS2 has no significant effect on sulfate levels.Our data suggest that miR395-targeted APS genes are key regulators of sulfate concentration in leaves.展开更多
Prorenin receptor （PRR） is a multi-functioning protein possessing at least four different roles： （1） working as a receptor for renin and prorenin producing angiotensin I from angiotensinogen thus enhancing the ti...Prorenin receptor （PRR） is a multi-functioning protein possessing at least four different roles： （1） working as a receptor for renin and prorenin producing angiotensin I from angiotensinogen thus enhancing the tissue renin-angiotensin system; （2） inducing intracellular signals when a ligand binds to PRR; （3） participating in the functions of vacuolar proton ATPase; and （4） constitut-ing the Wnt signaling receptor complex. Here, the roles of PRR in kidney physiology and diabetic conditions as well as recent fndings regarding a soluble form of PRR are discussed. We also propose the possible mechanism concerning diabetic nephropathy as “trade-off hypothe-sis” from a PRR point of view. In brief, under hypergly-cemic conditions, injured podocytes degrade degener-ated proteins and intracellular organelles which require V-ATPase and PRR for vesicle internal acidification. Sustained hyperglycemia overproduces PRR molecules, which are transported to the transmembrane and bind to increased serum prorenin in the diabetic condition. This enhances tissue renin-angiotensin system and PRR-mediated mitogen-activated protein kinase signals, resulting in increased injurious molecules such as transforming growth factor-β, cyclooxygenase2, interleukin1β, and tumor necrosis factor-α ending in diabetic ne-phropathy progression. Although many fndings led us to better PRR understanding, future works should elu-cidate which PRR functions, of the four discussed here, are dominant in each cell and kidney disease context.展开更多
文摘BACKGROUND The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases(V-ATPase)is located on chromosome Xq28.Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation(CDG).CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs.Therefore,the clinical presentation of patients with ATP6AP1-CDG varies widely.In this report,we present a case of ATP6AP1-CDG in a Chinese infant,with clinical features and genotype.CASE SUMMARY An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital.A post-admission examination at our hospital revealed abnormalities in the infant’s liver,brain,and immune system.Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A(p.E346K)in exon 9 of the ATP6AP1 gene.This variant of the ATP6AP1 gene has not been reported in East Asian countries until now.CONCLUSION Based on the infant’s clinical manifestations and the results of genetic detection,he was clearly diagnosed with ATP6AP1-CDG.The clinical manifestations of children with CDG vary widely.Genetic testing analysis helps in the clinical diagnosis of children with CDG.
基金the Arabidopsis Biological Resource Center for the support of T-DNA insertion mutantsthe support of the National Natural Science Foundation of China[Grant No.31100186]
文摘Sulfur nutrition is crucial for plant growth and development,as well as crop yield and quality.Inorganic sulfate in the soil is the major sulfur source for plants.After uptake,sulfate is activated by ATP sulfurylase,and then gets assimilated into sulfur-containing metabolites.However,the mechanism of regulation of sulfate levels by ATP sulfurylase is unclear.Here,we investigated the control of sulfate levels by miR395-mediated regulation of APS1/3/4.Sulfate was over-accumulated in the shoots of miR395 over-expression plants in which the expression of the APS1,APS3,and APS4 genes was suppressed.Accordingly,reduced expression of miR395 caused a decline of sulfate concentration.In agreement with these results,over-expression of the APS1,APS3,and APS4 genes led to the reduction of sulfate levels.Differential expression of these three APS genes in response to sulfate starvation implied that they have different functions.Further investigation revealed that the regulation of sulfate levels mediated by miR395 depends on the repression of its APS targets.Unlike the APS1,APS3,and APS4 genes,which encode plastid-localized ATP sulfurylases,the APS2 gene encodes a cytosolic version of ATP sulfurylase.Genetic analysis indicated that APS2 has no significant effect on sulfate levels.Our data suggest that miR395-targeted APS genes are key regulators of sulfate concentration in leaves.
文摘Prorenin receptor （PRR） is a multi-functioning protein possessing at least four different roles： （1） working as a receptor for renin and prorenin producing angiotensin I from angiotensinogen thus enhancing the tissue renin-angiotensin system; （2） inducing intracellular signals when a ligand binds to PRR; （3） participating in the functions of vacuolar proton ATPase; and （4） constitut-ing the Wnt signaling receptor complex. Here, the roles of PRR in kidney physiology and diabetic conditions as well as recent fndings regarding a soluble form of PRR are discussed. We also propose the possible mechanism concerning diabetic nephropathy as “trade-off hypothe-sis” from a PRR point of view. In brief, under hypergly-cemic conditions, injured podocytes degrade degener-ated proteins and intracellular organelles which require V-ATPase and PRR for vesicle internal acidification. Sustained hyperglycemia overproduces PRR molecules, which are transported to the transmembrane and bind to increased serum prorenin in the diabetic condition. This enhances tissue renin-angiotensin system and PRR-mediated mitogen-activated protein kinase signals, resulting in increased injurious molecules such as transforming growth factor-β, cyclooxygenase2, interleukin1β, and tumor necrosis factor-α ending in diabetic ne-phropathy progression. Although many fndings led us to better PRR understanding, future works should elu-cidate which PRR functions, of the four discussed here, are dominant in each cell and kidney disease context.
