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• W3198359218 abstract "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." @default.
• W3198359218 created "2021-09-13" @default.
• W3198359218 creator A5008078313 @default.
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• W3198359218 creator A5066749886 @default.
• W3198359218 creator A5066919739 @default.
• W3198359218 creator A5068897889 @default.
• W3198359218 date "2021-08-27" @default.
• W3198359218 modified "2023-10-16" @default.
• W3198359218 title "Long-term precision editing of neural circuits in mammals using engineered gap junction hemichannels" @default.
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