Tao Li, Coakley Sean, Shi Rebecca, Shen Kang
Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, CA, USA.
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Dev Cell. 2022 Jul 11;57(13):1615-1629.e3. doi: 10.1016/j.devcel.2022.05.019. Epub 2022 Jun 15.
Ligand-receptor interactions guide axon navigation and dendrite arborization. Mechanical forces also influence guidance choices. However, the nature of such mechanical stimulations, the mechanosensor identity, and how they interact with guidance receptors are unknown. Here, we demonstrate that mechanosensitive DEG/ENaC channels are required for dendritic arbor morphogenesis in Caenorhabditis elegans. Inhibition of DEG/ENaC channels causes reduced dendritic outgrowth and branching in vivo, a phenotype that is alleviated by overexpression of the mechanosensitive channels PEZO-1/Piezo or YVC1/TrpY1. DEG/ENaCs trigger local Ca transients in growing dendritic filopodia via activation of L-type voltage-gated Ca channels. Anchoring of filopodia by dendrite ligand-receptor complexes is required for the mechanical activation of DEG/ENaC channels. Therefore, mechanosensitive channels serve as a checkpoint for appropriate chemoaffinity by activating Ca transients required for neurite growth.
配体 - 受体相互作用引导轴突导航和树突分支。机械力也会影响导向选择。然而，这种机械刺激的性质、机械传感器的身份以及它们如何与导向受体相互作用尚不清楚。在这里，我们证明了机械敏感的DEG/ENaC通道是秀丽隐杆线虫树突分支形态发生所必需的。抑制DEG/ENaC通道会导致体内树突生长和分支减少，而机械敏感通道PEZO-1/Piezo或YVC1/TrpY1的过表达可缓解这一表型。DEG/ENaC通过激活L型电压门控钙通道在生长的树突丝状伪足中触发局部钙瞬变。树突配体 - 受体复合物对丝状伪足的锚定是DEG/ENaC通道机械激活所必需的。因此，机械敏感通道通过激活神经突生长所需的钙瞬变，作为适当化学亲和力的一个检查点。
