Sensory Research Center, CRI, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea.
Sensory Research Center, CRI, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea; College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Neuron. 2017 Apr 19;94(2):271-273.e2. doi: 10.1016/j.neuron.2017.03.038.
Mechanosensation is essential for various physiological processes, and it is mediated by mechanotransduction channels. Recently, we reported that TMEM150C/Tentonin 3 (TTN3) confers mechanically activated currents with slow inactivation kinetics in several cell types, including dorsal root ganglion neurons (Hong et al., 2016). The accompanying Matters Arising by Dubin, Murthy, and colleagues confirms that naive heterologous cells demonstrate a mechanically activated current, but finds that this response is absent in CRISPR-Cas9 Piezo1 knockout cell lines and suggests that TTN3 is a modulator of Piezo1. We present and discuss evidence based on co-expression of TTN3 and Peizo1 and mutant variants of the pore region of TTN3 to support that TTN3 is a pore-forming unit, not an amplifying adaptor for Piezo1 activity. This Matters Arising Response paper, along with Zhao et al. (2017), addresses the Matters Arising from Dubin et al. (2017), published concurrently in this issue of Neuron.
机械感觉对于各种生理过程至关重要，它是由机械转导通道介导的。最近，我们报道了 TMEM150C/Tentonin 3（TTN3）在包括背根神经节神经元在内的几种细胞类型中赋予具有缓慢失活动力学的机械激活电流（Hong 等人，2016）。Dubin、Murthy 及其同事的相关问题解答确认原始异源细胞表现出机械激活电流，但发现该反应在 CRISPR-Cas9 Piezo1 敲除细胞系中缺失，并表明 TTN3 是 Piezo1 的调节剂。我们提出并讨论了基于 TTN3 和 Piezo1 的共表达以及 TTN3 孔区突变体的证据，以支持 TTN3 是一种形成孔的单位，而不是 Piezo1 活性的放大接头。这篇问题解答论文，以及 Zhao 等人（2017），解决了同时发表在本期《神经元》上的 Dubin 等人（2017）的问题解答。
