连接蛋白
缝隙连接
生物
神经科学
生物神经网络
对接(动物)
细胞生物学
突变
计算生物学
生物化学
基因
突变
医学
细胞内
护理部
作者
Elizabeth Ransey,Kirill Chesnov,Elias Wisdom,Ryan Bowman,Tatiana Rodriguez,Elise Adamson,Gwenaëlle E. Thomas,Agustin Almoril-Porras,Hannah Schwennesen,Daniel A. Colón-Ramos,Rainbo Hultman,Nenad Bursac,Kafui Dzirasa
标识
DOI:10.1101/2021.08.24.457429
摘要
Summary The coordination of activity between brain cells is a key determinant of neural circuit function; nevertheless, approaches that selectively regulate communication between two distinct cellular components of a mammalian circuit remain sparse. To address this gap, we developed a novel class of gap junctions by selectively engineering two connexin proteins found in Morone americana (white perch fish): connexin34.7 (Cx34.7) and connexin35 (Cx35). By iteratively exploiting protein mutagenesis, a novel in vitro assay of connexin docking, and computational modeling of connexin hemichannel interactions, we uncovered a pattern of structural motifs that contribute to hemichannel docking compatibility. Targeting these motifs, we designed Cx34.7 and Cx35 hemichannels that dock with each other, but not with themselves, nor with other major connexins expressed in the mammalian central nervous system. We validated these hemichannels in vivo using C. elegans and mice, demonstrating that they can facilitate communication across neural circuits composed of pairs of distinct cell types and modify behavior accordingly. Thus, we establish a potentially translational approach, ‘ L ong-term in tegration of C ircuits using conne x ins’ (LinCx), for context-precise circuit-editing with unprecedented spatiotemporal specificity in mammals.
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