Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th...Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.展开更多
目的探讨Kank1基因在肺癌中的表达差异及其临床病理学意义。方法采用免疫组织化学方法,检测66例肺癌组织和20例正常肺组织中Kank1蛋白的表达,结合患者临床资料分析Kank1与肺癌发生发展的相关性。同时通过RT-PCR检测正常支气管上皮细胞...目的探讨Kank1基因在肺癌中的表达差异及其临床病理学意义。方法采用免疫组织化学方法,检测66例肺癌组织和20例正常肺组织中Kank1蛋白的表达,结合患者临床资料分析Kank1与肺癌发生发展的相关性。同时通过RT-PCR检测正常支气管上皮细胞与肺癌细胞中Kank1 m RNA的表达差异。结果Kank1基因在正常肺组织中的阳性表达率95.0%,其在肺癌组织中的阳性表达率为48.5%。Kank1在肺癌组织中的蛋白阳性表达率显著低于其在正常组织中的表达率(P<0.05);此外,其表达与患者有无淋巴结转移、年龄、性别、肿瘤病理分类及分化程度无关,且在正常支气管上皮细胞与肺癌细胞中Kank1 m RNA表达明显有差异。结论 Kank1在肺癌细胞及组织中表达降低,提示其表达下调与肺癌的发生发展密切相关。展开更多
基金supported by the National Key Research and Development Program of China,No.2021ZD0202503(to AHT)the National Natural Science Foundation of China,Nos.31872759(to AHT)and 32070707(to CF)+1 种基金Shenzhen Science and Technology Program,No.RCJC20210609104333007(to ZW)Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Fundamental Research Institutions,No.2021SHIBS0002(to ZW).
文摘Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
文摘目的探讨Kank1基因在肺癌中的表达差异及其临床病理学意义。方法采用免疫组织化学方法,检测66例肺癌组织和20例正常肺组织中Kank1蛋白的表达,结合患者临床资料分析Kank1与肺癌发生发展的相关性。同时通过RT-PCR检测正常支气管上皮细胞与肺癌细胞中Kank1 m RNA的表达差异。结果Kank1基因在正常肺组织中的阳性表达率95.0%,其在肺癌组织中的阳性表达率为48.5%。Kank1在肺癌组织中的蛋白阳性表达率显著低于其在正常组织中的表达率(P<0.05);此外,其表达与患者有无淋巴结转移、年龄、性别、肿瘤病理分类及分化程度无关,且在正常支气管上皮细胞与肺癌细胞中Kank1 m RNA表达明显有差异。结论 Kank1在肺癌细胞及组织中表达降低,提示其表达下调与肺癌的发生发展密切相关。
