【摘 要】
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Neurofilament light subunit (NFL) is the core component of neurofilaments, which are the main intermediate filaments (IF) in neurons.Many dominant inherited diseases are related to mutations in IF gen
【机 构】
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Department of Cell Biology, College of Life Sciences, Peking University, Beijing 100871, China
【出 处】
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中国神经科学学会第九届全国学术会议暨第五届会员代表大会
论文部分内容阅读
Neurofilament light subunit (NFL) is the core component of neurofilaments, which are the main intermediate filaments (IF) in neurons.Many dominant inherited diseases are related to mutations in IF genes.Recent studies report that NFL mutations are related to the charcot-marie-tooth (CMT) diseases, but the mechanism is unknown.Here, we show that seven 14-3-3 isoforms all interact with NFL, which is dependent on the phosphorylation of NFL head domain that is regulated by PKA.Site mutation analyses reveal many Serine phosphorylation sites in the head domain that are important for 14-3-3 binding.Mutations of these sites lead to aggregate formation.Moreover, 14-3-3 overexpression increases NFL exchange rate and leads to neurofilament disassembly.NFL mutations P8Q, P8L, P22S, found in CMT diseases, inhibit 14-3-3 binding and result in the formation of NFL aggregations, which can be rescued by 14-3-3 overexpression.Therefore, 14-3-3 proteins regulate NFL assembly and dynamic exchange through interaction with NFL, and can act as potential molecule targets for therapy of human CMT diseases.
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