The spectrin-based membrane skeleton is asymmetric and remodels during neural development in C. elegans
The spectrin-based membrane skeleton is asymmetric and remodels during neural development in C. elegans
复制标题
基于血影蛋白的膜骨架是不对称的，并且在秀丽隐杆线虫的神经发育过程中重塑
DOI：
10.1242/jcs.248583
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发表时间：
2020-08-01
影响因子：
4
通讯作者：
Ou, Guangshuo
中科院分区：
文献类型：
--
作者：
Jia, Ru;Chai, Yongping;Ou, Guangshuo
基于谱的膜力学扰动引起遗传性椭圆细胞增多症和脊髓小脑性共济失调，但发病的潜在细胞基础尚不清楚。在这里，我们将保守的与疾病相关的谱蛋白突变引入秀丽隐杆线虫基因组，并研究了谱蛋白对发育中的幼虫神经元迁移和树突形成的贡献。spectrin的缺失导致肌动蛋白在现有的前膜和次级膜突起外发生异位聚合，导致成年动物神经元定位和树突形态缺陷。Spectrin积聚在迁移的神经母细胞的外侧和后部，并从体细胞重新分布到新形成的树突中，表明基于Spectrin的膜骨架是不对称的，并在发育过程中重塑以调节肌动蛋白组装和细胞形状。我们从秀丽隐杆线虫中亲和纯化了spectrin，发现它的结合伴侣锚定蛋白与spectrin具有一定的功能。膜骨架的不对称和重塑可能使膜力学在不同发育事件中的时空调节成为可能。
Perturbation of spectrin-based membrane mechanics causes hereditary elliptocytosis and spinocerebellar ataxia, but the underlying cellular basis of pathogenesis remains unclear. Here, we introduced conserved disease-associated spectrin mutations into the Caenorhabditis elegans genome and studied the contribution of spectrin to neuronal migration and dendrite formation in developing larvae. The loss of spectrin resulted in ectopic actin polymerization outside of the existing front and secondary membrane protrusions, leading to defective neuronal positioning and dendrite morphology in adult animals. Spectrin accumulated in the lateral region and rear of migrating neuroblasts and redistributes from the soma into the newly formed dendrites, indicating that the spectrin-based membrane skeleton is asymmetric and remodels to regulate actin assembly and cell shape during development. We affinity-purified spectrin from C. elegans and showed that its binding partner ankyrin functions with spectrin. Asymmetry and remodeling of the membrane skeleton might enable spatiotemporal modulation of membrane mechanics for distinct developmental events.