Fast structural responses of gap junction membrane domains to AB5 toxins

Irina V. Majoul, Liang Gao, Eric Betzig, Daria Onichtchouk, Eugenia Butkevich, Yuri Kozlov, Feliksas Bukauskas, Michael V.L. Bennett, Jennifer Lippincott-Schwartz, Rainer Duden

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9 Scopus citations

Abstract

Gap junctions (GJs) represent connexin-rich membrane domains that connect interiors of adjoining cells in mammalian tissues. How fast GJs can respond to bacterial pathogens has not been known previously. Using Bessel beam plane illumination and confocal spinning disk microscopy, we found fast (∼500 ms) formation of connexin-depleted regions (CDRs) inside GJ plaques between cells exposed to AB5 toxins. CDR formation appears as a fast redistribution of connexin channels within GJ plaques with minor changes in outline or geometry. CDR formation does not depend on membrane trafficking or submembrane cytoskeleton and has no effect on GJ conductance. However, CDR responses depend on membrane lipids, can be modified by cholesterol-clustering agents and extracellular K+ ion concentration, and influence cAMP signaling. The CDR response of GJ plaques to bacterial toxins is a phenomenon observed for all tested connexin isoforms. Through signaling, the CDR response may enable cells to sense exposure to AB5 toxins. CDR formation may reflect lipid-phase separation events in the biological membrane of the GJ plaque, leading to increased connexin packing and lipid reorganization. Our data demonstrate very fast dynamics (in the millisecond-To-second range) within GJ plaques, which previously were considered to be relatively stable, long-lived structures.

Original languageEnglish (US)
Pages (from-to)E4125-E4133
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number44
DOIs
StatePublished - Oct 29 2013

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Majoul, I. V., Gao, L., Betzig, E., Onichtchouk, D., Butkevich, E., Kozlov, Y., Bukauskas, F., Bennett, M. V. L., Lippincott-Schwartz, J., & Duden, R. (2013). Fast structural responses of gap junction membrane domains to AB5 toxins. Proceedings of the National Academy of Sciences of the United States of America, 110(44), E4125-E4133. https://doi.org/10.1073/pnas.1315850110