Varandas Katherine C, Hodges Brianna M, Lubeck Lauren, Farinas Amelia, Liang Yupu, Lu Yun, Shaham Shai
bioRxiv. 2023 Nov 17:2023.11.16.567404. doi: 10.1101/2023.11.16.567404.
Neurons have elaborate structures that determine their connectivity and functions. Changes in neuronal structure accompany learning and memory formation and are hallmarks of neurological disease. Here we show that glia monitor dendrite structure and respond to dendrite perturbation. In mutants with defective sensory-organ dendrite cilia, adjacent glia accumulate extracellular matrix-laden vesicles, secrete excess matrix around cilia, alter gene expression, and change their secreted protein repertoire. Inducible cilia disruption reveals that this response is acute. DGS-1, a 7-transmembrane domain neuronal protein, and FIG-1, a multifunctional thrombospondin-domain glial protein, are required for glial detection of cilia integrity, and exhibit mutually-dependent localization to and around cilia, respectively. While inhibiting glial secretion disrupts dendritic cilia properties, hyperactivating the glial response protects against dendrite damage. Our studies uncover a homeostatic protective dendrite-glia interaction and suggest that similar signaling occurs at other sensory structures and at synapses, which resemble sensory organs in architecture and molecules.
神经元具有复杂的结构,这些结构决定了它们的连接性和功能。神经元结构的变化伴随着学习和记忆的形成,并且是神经疾病的标志。在这里,我们表明神经胶质细胞监测树突结构并对树突扰动做出反应。在感觉器官树突纤毛有缺陷的突变体中,相邻的神经胶质细胞积累富含细胞外基质的囊泡,在纤毛周围分泌过量的基质,改变基因表达,并改变它们分泌的蛋白质库。可诱导的纤毛破坏表明这种反应是急性的。DGS-1是一种7跨膜结构域的神经元蛋白,而FIG-1是一种多功能血小板反应蛋白结构域的神经胶质蛋白,它们是神经胶质细胞检测纤毛完整性所必需的,并且分别在纤毛及其周围表现出相互依赖的定位。虽然抑制神经胶质细胞分泌会破坏树突纤毛的特性,但过度激活神经胶质细胞反应可防止树突损伤。我们的研究揭示了一种稳态保护性的树突-神经胶质细胞相互作用,并表明类似信号在其他感觉结构和突触处发生,这些结构在结构和分子上类似于感觉器官。