Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Lewis-Sigler Institute, Princeton University, Princeton, New Jersey, United States of America.
PLoS Genet. 2020 Dec 28;16(12):e1009235. doi: 10.1371/journal.pgen.1009235. eCollection 2020 Dec.
Dendritic arbor morphology influences how neurons receive and integrate extracellular signals. We show that the ELAV/Hu family RNA-binding protein Found in neurons (Fne) is required for space-filling dendrite growth to generate highly branched arbors of Drosophila larval class IV dendritic arborization neurons. Dendrites of fne mutant neurons are shorter and more dynamic than in wild-type, leading to decreased arbor coverage. These defects result from both a decrease in stable microtubules and loss of dendrite-substrate interactions within the arbor. Identification of transcripts encoding cytoskeletal regulators and cell-cell and cell-ECM interacting proteins as Fne targets using TRIBE further supports these results. Analysis of one target, encoding the cell adhesion protein Basigin, indicates that the cytoskeletal defects contributing to branch instability in fne mutant neurons are due in part to decreased Basigin expression. The ability of Fne to coordinately regulate the cytoskeleton and dendrite-substrate interactions in neurons may shed light on the behavior of cancer cells ectopically expressing ELAV/Hu proteins.
树突形态影响神经元如何接收和整合细胞外信号。我们表明，神经元中发现的 ELAV/Hu 家族 RNA 结合蛋白 Found in neurons (Fne) 对于空间填充树突生长是必需的，以产生果蝇幼虫 IV 类树突状分枝神经元的高度分支树突。fne 突变神经元的树突比野生型短且更具动态性，导致树突覆盖范围减小。这些缺陷既源于稳定微管的减少，也源于树突-基质相互作用的丧失。使用 TRIBE 鉴定编码细胞骨架调节剂和细胞-细胞以及细胞-细胞外基质相互作用蛋白的转录本作为 Fne 的靶标进一步支持了这些结果。对一个靶标（编码细胞黏附蛋白 Basigin）的分析表明，导致 fne 突变神经元中分支不稳定性的细胞骨架缺陷部分归因于 Basigin 表达的减少。Fne 协调调节神经元中细胞骨架和树突-基质相互作用的能力可能阐明异位表达 ELAV/Hu 蛋白的癌细胞的行为。
