Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, McGovern Institute for Brain Research, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
J Cell Sci. 2020 Aug 5;133(15):jcs248583. doi: 10.1242/jcs.248583.
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 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 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.
基于血影蛋白的膜力学的扰动会导致遗传性椭圆形红细胞增多症和脊髓小脑共济失调，但发病机制的潜在细胞基础仍不清楚。在这里，我们将保守的疾病相关血影蛋白突变引入基因组，并研究了血影蛋白对发育中幼虫神经元迁移和树突形成的贡献。血影蛋白的缺失导致现有前缘和次级膜突起之外的肌动蛋白异常聚合，导致成年动物神经元定位和树突形态缺陷。血影蛋白在迁移神经母细胞的侧区和后部积累，并从体部重新分布到新形成的树突中，表明基于血影蛋白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 中亲和纯化了血影蛋白，并表明其结合伴侣锚蛋白与血影蛋白相互作用。膜骨架的不对称性和重塑可能使膜力学在不同的发育事件中具有时空调节能力。
