Department of Biochemistry and Cell Biology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755.
Mol Biol Cell. 2023 Apr 1;34(4):ar26. doi: 10.1091/mbc.E22-06-0219. Epub 2023 Feb 8.
Ciliary length is highly regulated, but can be disrupted by lithium, which causes ciliary elongation across cell types and organisms. We used the algal system to investigate the mechanism behind lithium-induced ciliary elongation. Protein synthesis is not required for lengthening, and the target of lithium, GSK3, has substrates that can influence membrane dynamics. Further, ciliary assembly requires a supply of ciliary membrane as well as protein. Lithium-treated cilia elongate normally with brefeldin treatment, but dynasore treatment produced defective lengthening suggesting a source of membrane from the cell surface rather than the Golgi. Genetic or chemical perturbation of the Arp2/3 complex or dynamin, required for endocytosis, blocks lithium-induced ciliary lengthening. Finally, we found an increase in Arp2/3 complex- and endocytosis-dependent actin filaments near the ciliary base upon lithium treatment. Our results identify a mechanism for lithium-mediated cilium lengthening and demonstrate the endocytic pathway for cilium membrane supply in algae is likely a conserved mechanism given lithium's conserved effects across organisms.
纤毛长度受到高度调控，但锂会破坏纤毛，导致跨细胞类型和生物体的纤毛伸长。我们使用藻类系统来研究锂诱导纤毛伸长的机制。蛋白质合成不是伸长所必需的，而锂的靶标 GSK3 有可以影响膜动力学的底物。此外，纤毛组装需要纤毛膜以及蛋白质的供应。用布雷菲德菌素处理锂处理的纤毛可以正常伸长，但dynasore 处理产生了有缺陷的伸长，表明膜来自细胞表面而不是高尔基体。内吞作用所需的 Arp2/3 复合物或 dynamin 的遗传或化学干扰会阻止锂诱导的纤毛伸长。最后，我们发现锂处理后靠近纤毛基部的 Arp2/3 复合物和内吞作用依赖的肌动蛋白丝增加。我们的结果确定了锂介导的纤毛伸长的机制，并证明了藻类中纤毛膜供应的内吞途径可能是一种保守的机制，因为锂在生物体中具有保守的作用。
