LMNA突变介导细胞核结构与功能异常

LMNA Mutation Result in the Structural and Functional Abnormal of Nuclear Envelope

核膜蛋白综合征是一类主要由细胞核膜结构蛋白(如lamins、SUNs、emerin等)基因突变诱发的包括早衰等一系列疾病的总称,因其多数突变发现于核纤层蛋白基因上,所以又被称为核纤层蛋白综合征,其发病机制目前还不清楚。本文以A型核纤层蛋白基因位点上的致病突变基因C1294T为切入点,研究突变对细胞核结构与功能的影响,以及相关核膜蛋白及染色质定位与功能的影响。研究结果表明,LMNA突变对细胞核膜的结构与功能完整性具有影响作用,可致使细胞核膜异形甚至产生凸起小泡;另外还对细胞核内染色质的定位具有一定抑制作用,使其在细胞核内形成不均匀的分布状态,表明该突变已经影响到细胞核正常的结构与功能,并可能进一步诱发相关疾病。

Nuclear envelope proteins syndrome is an umbrella term of a series of human diseases induced by kinds of nuclear envelope structural proteins（lamins,SUNs,emerin,etc.）gene mutations,such as progeria.Due to the majority of mutations found in LMNA gene,these diseases are also named laminopathies,but their pathogenesis is still unclear.So the lamin A gene mutation C1294 T was taken as a candidate to study the effect of gene mutations on the structure and function of cell nucleus and on the localization and function of related chromatin and nuclear membrane proteins.The research results showed that the LMNA mutation affected the integrity of structure and function of nuclear envelope,even resulted in the nuclear envelope wrinkle and shaped vesicles.In addition,the mutation had a certain inhibiting effect on the localization of chromatin in cell nucleus and the uneven distribution ofchromosome in the nucleus.In conclusion,the LMNA mutation might affect the normal structure and function of nuclear envelope,and could further induce related diseases.