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TNFAIP1与RIN3相互作用的鉴定 被引量:1
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作者 贺琼芝 李莉 +5 位作者 颜峰 李文 魏科 刘庆文 张健 胡翔 《湖南师范大学自然科学学报》 CAS 北大核心 2010年第3期83-87,共5页
TNFAIP1是第一个被鉴定能受TNF-α(tumor necrosis factor-α)诱导的蛋白.TNFAIP1基因是一个多功能基因,参与DNA的复制和修复,细胞周期的调控,细胞信号通路转导的调节等.采用酵母双杂交的方法以TN-FAIP1为靶蛋白筛选得到与其相互作用蛋... TNFAIP1是第一个被鉴定能受TNF-α(tumor necrosis factor-α)诱导的蛋白.TNFAIP1基因是一个多功能基因,参与DNA的复制和修复,细胞周期的调控,细胞信号通路转导的调节等.采用酵母双杂交的方法以TN-FAIP1为靶蛋白筛选得到与其相互作用蛋白RIN3.RIN3含有RIN家族多个多功能的结构域,根据RIN3结构域对其分段,研究与TNFAIP1的相互作用.通过免疫共沉淀,荧光共定位一系列细胞证明TNFAIP1蛋白能直接与RIN3相互作用,提示TNFAIP1可能参与细胞的胞吞胞吐. 展开更多
关键词 TNFAIP1 rin3 酵母双杂交 相互作用
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Upregulation of RIN3 induces endosomal dysfunction in Alzheimer’s disease 被引量:1
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作者 Ruinan Shen Xiaobei Zhao +11 位作者 Lu He Yongbo Ding Wei Xu Suzhen Lin Savannah Fang Wanlin Yang Kijung Sung Brian Spencer Robert A.Rissman Ming Lei Jianqing Ding Chengbiao Wu 《Translational Neurodegeneration》 SCIE CAS 2020年第2期290-308,共19页
Background In Alzheimer’s Disease(AD),about one-third of the risk genes identified by GWAS encode proteins that function predominantly in the endocytic pathways.Among them,the Ras and Rab Interactor 3(RIN3)is a guani... Background In Alzheimer’s Disease(AD),about one-third of the risk genes identified by GWAS encode proteins that function predominantly in the endocytic pathways.Among them,the Ras and Rab Interactor 3(RIN3)is a guanine nucleotide exchange factor(GEF)for the Rab5 small GTPase family and has been implicated to be a risk factor for both late onset AD(LOAD)and sporadic early onset AD(sEOAD).However,how RIN3 is linked to AD pathogenesis is currently undefined.Methods Quantitative PCR and immunoblotting were used to measure the RIN3 expression level in mouse brain tissues and cultured basal forebrain cholinergic neuron(BFCNs).Immunostaining was used to define subcellular localization of RIN3 and to visualize endosomal changes in cultured primary BFCNs and PC12 cells.Recombinant flag-tagged RIN3 protein was purified from HEK293T cells and was used to define RIN3-interactomes by mass spectrometry.RIN3-interacting partners were validated by co-immunoprecipitation,immunofluorescence and yeast two hybrid assays.Live imaging of primary neurons was used to examine axonal transport of amyloid precursor protein(APP)andβ-secretase 1(BACE1).Immunoblotting was used to detect protein expression,processing of APP and phosphorylated forms of Tau.Results We have shown that RIN3 mRNA level was significantly increased in the hippocampus and cortex of APP/PS1 mouse brain.Basal forebrain cholinergic neurons(BFCNs)cultured from E18 APP/PS1 mouse embryos also showed increased RIN3 expression accompanied by early endosome enlargement.In addition,via its proline rich domain,RIN3 recruited BIN1(bridging integrator 1)and CD2AP(CD2 associated protein),two other AD risk factors,to early endosomes.Interestingly,overexpression of RIN3 or CD2AP promoted APP cleavage to increase its carboxyl terminal fragments(CTFs)in PC12 cells.Upregulation of RIN3 or the neuronal isoform of BIN1 increased phosphorylated Tau level.Therefore,upregulation of RIN3 expression promoted accumulation of APP CTFs and increased phosphorylated Tau.These effects by RIN3 was rescued by the expression of a dominant negative Rab5(Rab5S34N)construct.Our study has thus pointed to that RIN3 acts through Rab5 to impact endosomal trafficking and signaling.Conclusion RIN3 is significantly upregulated and correlated with endosomal dysfunction in APP/PS1 mouse.Through interacting with BIN1 and CD2AP,increased RIN3 expression alters axonal trafficking and procession of APP.Together with our previous studies,our current work has thus provided important insights into the role of RIN3 in regulating endosomal signaling and trafficking. 展开更多
关键词 Alzheimer's disease(AD) AD risk factors ENDOSOMES TRAFFICKING rin3 BIN1 CD2AP Tau
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