細胞間通信の新たな構成要素を発見―「キャップ構造」が電気的シナプスを制御する可能性(New Building Blocks of Cell Communication: How an Invisible “Cap” could control Electrical Synapses)

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2025-12-01 ゲーテ大学

ゲーテ大学フランクフルトらの国際研究チームは、生細胞内の電気的シナプス(ギャップ結合)をクライオ電子トモグラフィーで観察し、チャネルの細胞内側に存在する「見えないキャップ構造」を発見した。キャップはUNC-1タンパク質により形成される可能性が高く、シミュレーションでもチャネル上に安定して配置され相互作用できることが確認された。これにより、電気シナプスは単純な“常に開いた通路”ではなく、キャップによって開閉や強度調整が行われる可能性が示唆された。心臓・腸管・神経系など、細胞間の電気的同期が重要な組織において、新たな制御原理となり得るほか、細胞間通信異常に関わる疾患の治療標的としても期待されるという。

細胞間通信の新たな構成要素を発見―「キャップ構造」が電気的シナプスを制御する可能性(New Building Blocks of Cell Communication: How an Invisible “Cap” could control Electrical Synapses)
Top row: The cryo-ET averages of the gap junction channels (left) revealed striking caps (right; purple) on the inside of the cell. Bottom row: The gap junctions (light blue) allow cells to communicate across their membranes (gray) (Image: N. Rosenkranz).

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ギャップジャンクション-ストマチン複合体のin situ構造 In situ structure of a gap junction–stomatin complex

Nils Rosenkranz, Alexandra N. Birtasu, Konstantin Wieland, Lisa Rehm, […] , and Alexander Gottschalk
Science Advances  Published:5 Nov 2025
DOI:https://doi.org/10.1126/sciadv.aea8596

Abstract

Gap junctions (GJs) are intercellular channels that mediate electrical signals and transfer of small molecules. They are crucial for brain, heart, and other organ functions. While molecular structures of purified homomeric GJs are available, information of in situ structures is lacking. In vivo, GJs can form heteromers with different functionalities and may associate with other proteins. Here, we analyzed Caenorhabditis elegans GJs by cryo–electron tomography and subtomogram averaging. We observed hexagonal arrays of GJs at cellular junctions in primary embryonal cells that displayed distinct wide and narrow conformations. Moreover, we found a cap-like, cytosolic protein assembly enclosing the channel pore. We propose that the cap is formed by the stomatin UNC-1, known to interact with UNC-9 innexins. This is corroborated by matching AlphaFold3 models of UNC-1 multimers with our subtomogram average structure; by expressing GFP-tagged UNC-1, leading to cap structures with additional density; and by coarse-grained MD simulations. UNC-1/stomatin rings may affect GJ formation or functions, possibly beyond nematodes.

生物工学一般
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