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Unlike preschoolers, cells are good about sharing. They swap ions, nutrients, and other molecules via membrane channels called gap junctions. But on page 881, van Zeijl et al. show that local loss of a phospholipid permits cells to become selfish and shut the channels.

Open gap junctions are crucial for heart contraction, wound repair, and other functions. But cells can temporarily shut the channels—when injured, for instance—and cancer cells can shut them permanently. G protein–coupled receptors close these portals, which are often made from the protein connexin43. But how that closure happens was unclear.

G protein–coupled receptors latch onto the enzyme PLCß, which in turn slices up the membrane phospholipid PIP₂. The researchers found that blocking PLCß or cranking up PIP₂ production kept the channels open, suggesting that PIP₂'s digestion helped close them. To confirm the conclusion, van Zeijl et al. used a two-part, PIP₂-cutting enzyme that assembles on the membrane only after a dose of the drug rapamycin. Adding the compound shut gap junctions.

How PIP₂ influences channels was initially mysterious, as it did not attach to connexin43. But the group discovered that PLCß hooked onto the protein ZO-1, which does link to connexin43. The results suggest a mechanism in which ZO-1 positions PLCß so that it can chop up PIP₂ near connexin43. The next step remains unclear. Presumably, PIP₂ breakdown stimulates a protein that nudges the junction closed, but its identity is unknown.

Mitch Leslie

mitchleslie{at}comcast.net

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Related Article

Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate

Leonie van Zeijl, Bas Ponsioen, Ben N.G. Giepmans, Aafke Ariaens, Friso R. Postma, Péter Várnai, Tamas Balla, Nullin Divecha, Kees Jalink, and Wouter H. Moolenaar
J. Cell Biol. 2007 177: 881-891. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Related Collections Related Article Social Bookmarking                      What's this?