Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.
J Neurosci. 2013 Jan 16;33(3):936-49. doi: 10.1523/JNEUROSCI.2749-12.2013.
Neuronal DEG/ENaC (degenerin and epithelial Na(+) channel) Na(+) channels have been implicated in touch sensation. For example, MEC-4 is expressed in touch neurons in Caenorhabditis elegans and mediates gentle-touch response. Similarly, homologous mammalian ASIC2 and ASIC3 are expressed in sensory neurons and produce touch phenotypes when knocked out in mice. Here, we show that novel DEG/ENaC subunits DELM-1 and DELM-2 (degenerin-like channel mechanosensory linked-1 and degenerin-like channel mechanosensory linked-2) are expressed in glia associated with touch neurons in C. elegans and that their knock-out causes defects in mechanosensory behaviors related to nose touch and foraging, which are mediated by OLQ and IL1 sensory neurons. Cell-specific rescue supports that DELM-1 and DELM-2 are required cell-autonomously in glia to orchestrate mechanosensory behaviors. Electron microscopy reveals that in delm-1 knock-outs, OLQ and IL1 sensory neurons and associated glia are structurally normal. Furthermore, we show that knock-out of DELM-1 and DELM-2 does not disrupt the expression or cellular localization of TRPA-1, a TRP channel needed in OLQ and IL1 neurons for touch behaviors. Rather, rescue of the delm-1 nose-touch-insensitive phenotype by expression of a K(+) channel in socket glia and of a cationic channel in OLQ neurons suggests that DELM channels set basal neuronal excitability. Together, our data show that DELM-1 and DELM-2 are expressed in glia associated with touch neurons where they are not needed for neuronal structural integrity or cellular distribution of neuronal sensory channels, but rather for their function.
神经元 DEG/ENaC（退行性和上皮钠离子通道）钠离子通道与触觉有关。例如，MEC-4 在秀丽隐杆线虫的触神经元中表达，并介导轻触反应。类似地，同源的哺乳动物 ASIC2 和 ASIC3 在感觉神经元中表达，当在小鼠中敲除时会产生触觉表型。在这里，我们表明，新型 DEG/ENaC 亚基 DELM-1 和 DELM-2（退行性通道机械敏感相关-1 和退行性通道机械敏感相关-2）在与线虫触神经元相关的神经胶质细胞中表达，并且它们的敲除导致与嗅觉神经元相关的触觉行为缺陷和觅食行为缺陷，这些行为是由 OLQ 和 IL1 感觉神经元介导的。细胞特异性拯救支持 DELM-1 和 DELM-2 在胶质细胞中需要细胞自主性来协调机械感觉行为。电子显微镜显示，在 delm-1 敲除体中，OLQ 和 IL1 感觉神经元及其相关神经胶质细胞的结构正常。此外，我们表明，DELM-1 和 DELM-2 的敲除不会破坏 TRPA-1 的表达或细胞定位，TRPA-1 是 OLQ 和 IL1 神经元中触行为所必需的 TRP 通道。相反，通过在插座神经胶质细胞中表达 K+通道和在 OLQ 神经元中表达阳离子通道来拯救 delm-1 鼻子触觉不敏感表型表明 DELM 通道设定了基础神经元兴奋性。总之，我们的数据表明，DELM-1 和 DELM-2 在与触神经元相关的神经胶质细胞中表达，它们不需要神经元结构完整性或神经元感觉通道的细胞分布，而是需要它们的功能。
