报告中国汉族人群首例VAMP2基因突变致伴有肌张力低下的神经发育障碍和自闭症特征伴或不伴运动过度病(neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements,NEDHAHM),以期为临...报告中国汉族人群首例VAMP2基因突变致伴有肌张力低下的神经发育障碍和自闭症特征伴或不伴运动过度病(neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements,NEDHAHM),以期为临床诊治提供借鉴。患儿为14岁女童,以精神行为异常起病,表现为少言少语,基因检测提示VAMP2基因的3号外显子c.166C>T(p.Arg56Ter)杂合突变。对国外同类报告中12例患者资料回顾后发现,该病多在婴幼儿时期发病,男性多于女性,临床预后不佳,4-氨基吡啶可能为此病潜在性治疗药物,可改善患者症状。展开更多
The whole length SPV2 gene of 715 bp, encoding VAMP-2 protein of 110 amino acids from Japanese sea perch, Lateolabrax japonicus, was obtained by using both RT-PCR; anchored PCR strategies while we initiated the struct...The whole length SPV2 gene of 715 bp, encoding VAMP-2 protein of 110 amino acids from Japanese sea perch, Lateolabrax japonicus, was obtained by using both RT-PCR; anchored PCR strategies while we initiated the structural; functional study on SNARE proteins in marine teleostean. Analysis of the deduced amino acid sequence indicated that SPV2 has its core arginine residue, a potential N-linked glycosylation site near its N-terminal,; one transmembrane domain in its C-terminal. Advanced structural analysis of bioinformatics approach predicts a coiled-coil α-helix backbone as the characteristic of SPV2 main conformational structure, identical to the structure of rat VAMP-2 obtained by crystallography. Semi-quantitative RT-PCR revealed that SPV2 was generally expressed in 10 neural; non-neural tissues, with the highest concentration in brain; the least in muscle.展开更多
Excessive demand for translation and protein folding in the endoplasmic reticulum(ER) can cause ER stress in plants. Here, we show that CALRETICULIN 1(CRT1) and CRT2 are critical components in the accumulation of VESI...Excessive demand for translation and protein folding in the endoplasmic reticulum(ER) can cause ER stress in plants. Here, we show that CALRETICULIN 1(CRT1) and CRT2 are critical components in the accumulation of VESICLE-ASSOCIATED MEMBRANE PROTEIN 721(VAMP721) and VAMP722 during ER stress responses. We show that CRT2 interacts with VAMP722 and that CRT1/2 post-translationally maintain elevated VAMP721/722 levels under ER stress.The greater growth inhibition in VAMP721/722-deficient plants, induced by tunicamycin, suggests that plants under ER stress maintain physiological homeostasis, at least in part, by regulating VAMP721/722 levels, as VAMP721/722 are known to participate in various biological processes.展开更多
The production and secretion of antibodies by human plasma cells(PCs)are two essential processes of humoral immunity.The secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive fact...The production and secretion of antibodies by human plasma cells(PCs)are two essential processes of humoral immunity.The secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors(SNAREs),which are located in the plasma membrane(t-SNAREs)and in the antibody-carrying vesicle membrane(v-SNARE),and mediate the fusion of both membranes.We have previously shown that SNAP23 and STX4 are the t-SNAREs responsible for antibody secretion.Here,using human PCs and antibody-secreting cell lines,we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein(VAMP)isoforms,demonstrating that all isoforms(with the exception of VAMP1)are expressed by the referenced cells.Furthermore,the functional role in antibody secretion of each expressed VAMP isoform was tested using siRNA.Our results show that VAMP2 may be the v-SNARE involved in vesicular antibody release.To further support this conclusion,we used tetanus toxin light chain to cleave VAMP2,conducted experiments to verify co-localization of VAMP2 in antibody-carrying vesicles,and demonstrated the coimmunoprecipitation of VAMP2 with STX4 and SNAP23 and the in situ interaction of VAMP2 with STX4.Taken together,these findings implicate VAMP2 as the main VAMP isoform functionally involved in antibody secretion.展开更多
文摘报告中国汉族人群首例VAMP2基因突变致伴有肌张力低下的神经发育障碍和自闭症特征伴或不伴运动过度病(neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements,NEDHAHM),以期为临床诊治提供借鉴。患儿为14岁女童,以精神行为异常起病,表现为少言少语,基因检测提示VAMP2基因的3号外显子c.166C>T(p.Arg56Ter)杂合突变。对国外同类报告中12例患者资料回顾后发现,该病多在婴幼儿时期发病,男性多于女性,临床预后不佳,4-氨基吡啶可能为此病潜在性治疗药物,可改善患者症状。
基金supported by the National Natural Science Foundation of China(Grant No.40476060)Hi-Tech Research and Development Program of China(Grant No.2002AA629120).
文摘The whole length SPV2 gene of 715 bp, encoding VAMP-2 protein of 110 amino acids from Japanese sea perch, Lateolabrax japonicus, was obtained by using both RT-PCR; anchored PCR strategies while we initiated the structural; functional study on SNARE proteins in marine teleostean. Analysis of the deduced amino acid sequence indicated that SPV2 has its core arginine residue, a potential N-linked glycosylation site near its N-terminal,; one transmembrane domain in its C-terminal. Advanced structural analysis of bioinformatics approach predicts a coiled-coil α-helix backbone as the characteristic of SPV2 main conformational structure, identical to the structure of rat VAMP-2 obtained by crystallography. Semi-quantitative RT-PCR revealed that SPV2 was generally expressed in 10 neural; non-neural tissues, with the highest concentration in brain; the least in muscle.
基金supported by grants from the National Research Foundation (2017R1D1A1B 03029802 to H.S.Y., and 2016R1D1A1B02007322 to C.K.)the Strategic Initiative for Microbiomes in Agriculture and Food, Ministry of Agriculture, Food and Rural Affairs (916007-02-1-HD020 to C.K.) Korea
文摘Excessive demand for translation and protein folding in the endoplasmic reticulum(ER) can cause ER stress in plants. Here, we show that CALRETICULIN 1(CRT1) and CRT2 are critical components in the accumulation of VESICLE-ASSOCIATED MEMBRANE PROTEIN 721(VAMP721) and VAMP722 during ER stress responses. We show that CRT2 interacts with VAMP722 and that CRT1/2 post-translationally maintain elevated VAMP721/722 levels under ER stress.The greater growth inhibition in VAMP721/722-deficient plants, induced by tunicamycin, suggests that plants under ER stress maintain physiological homeostasis, at least in part, by regulating VAMP721/722 levels, as VAMP721/722 are known to participate in various biological processes.
基金This work was supported by grants from the Spanish National Institute of Health‘Carlos III’(FIS-PI1101091,FIS-PI071075)from Plan Nacional I+D+i 2008-2011 from Fondos Europeos de Desarrollo Regional(FEDER)the Consejería de Innovación,Ciencia y Empresa-Junta de Andalucía(P09-CTS-5445)to AC-C and an ASPiRE grant from Ball State University(Indiana,USA)to MK-W.
文摘The production and secretion of antibodies by human plasma cells(PCs)are two essential processes of humoral immunity.The secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors(SNAREs),which are located in the plasma membrane(t-SNAREs)and in the antibody-carrying vesicle membrane(v-SNARE),and mediate the fusion of both membranes.We have previously shown that SNAP23 and STX4 are the t-SNAREs responsible for antibody secretion.Here,using human PCs and antibody-secreting cell lines,we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein(VAMP)isoforms,demonstrating that all isoforms(with the exception of VAMP1)are expressed by the referenced cells.Furthermore,the functional role in antibody secretion of each expressed VAMP isoform was tested using siRNA.Our results show that VAMP2 may be the v-SNARE involved in vesicular antibody release.To further support this conclusion,we used tetanus toxin light chain to cleave VAMP2,conducted experiments to verify co-localization of VAMP2 in antibody-carrying vesicles,and demonstrated the coimmunoprecipitation of VAMP2 with STX4 and SNAP23 and the in situ interaction of VAMP2 with STX4.Taken together,these findings implicate VAMP2 as the main VAMP isoform functionally involved in antibody secretion.
