#NIHFundedDiscovery How do cells avoid the "kiss of death"? Gap junctions share life-saving signals—but under stress, they shut down to prevent spreading cytotoxic damage. #CryoEM reveals the molecular switches behind this process! www.biorxiv.org/content/10.1... www.biorxiv.org/content/10.1... - ThreadSky

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reichowlab.bsky.social • 1 day ago

#NIHFundedDiscovery

How do cells avoid the "kiss of death"?

Gap junctions share life-saving signals—but under stress, they shut down to prevent spreading cytotoxic damage.

#CryoEM reveals the molecular switches behind this process!

https://www.biorxiv.org/content/10.1101/2025.02.12.637953v1

https://www.biorxiv.org/content/10.1101/2025.02.12.637955v1

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spirabo.bsky.social•1 day ago

It seems connexins might also be therapeutic targets in migraine and MS.

reichowlab.bsky.social•1 day ago

In our first study, harnessing native Cx46/50 gap junctions, we provide the first atomic-level view of pH gating. Under acidic conditions, lipids infiltrate the pore, displacing the NT domain and reversibly closing the channel.

https://www.biorxiv.org/content/10.1101/2025.02.12.637953v1

reichowlab.bsky.social•1 day ago

In our second study, we resolve how calcium shuts down gap junctions. Novel Ca²⁺ binding sites are identified in the pore that trigger NT domain movements, leading to pore collapse/closure – supporting the classic "iris model" of gating proposed over 40 years ago!

https://www.biorxiv.org/content/10.1101/2025.02.12.637955v1

reichowlab.bsky.social•1 day ago

Together, these works provide a unified framework for understanding how connexins respond to cellular stress – offering new insights into cataract formation, ischemia, and connexin-related diseases.

reichowlab.bsky.social•1 day ago

These studies wouldn’t have been possible without support from the #NIH, the incredible efforts of my lab at #OHSU, the support of #PNCC, our local Cryo-EM core facility, and our amazing structural biology & #CryoEM community. Huge thanks to everyone who contributed!

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