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Charged signaling

A probe detecting surface charge (red) is depleted during phagocytosis. GRINSTEIN/AAAS

Areas of negative charge come and go on the plasma membrane, report Tony Yeung, Sergio Grinstein (Hospital for Sick Children, Toronto, Canada), and colleagues. Loss of the charged areas correlates with the loss of certain signaling proteins from the membrane and inactivation of related downstream activity.

Attraction based on charge is well established for sequence-specific protein–protein interactions. But the Toronto group documented an electrostatic switch that was evident with many different probes, with many different anionic lipids, and on liposomes that lacked any proteins. The probes were modeled on fragments of the K-Ras protein and combined polycationic sequences with a hydrophobic anchor to keep the probe in the plasma membrane rather than interacting with the anionic nucleoplasm.

The probes were displaced from the intracellular face of the plasma membrane by three different conditions: an influx of calcium; flipping out of negatively charged phosphatidylserine (PS); and the later stages of phagocytosis. Rac1 dissociated from phagosomes with similar kinetics, even if locked in a GTP-bound form.

During phagocytosis, signaling results in hydrolysis of negatively charged membrane-localized PIP2 to form uncharged diacylglycerol and cytoplasmic IP3. Inhibition of PIP2 hydrolysis reduced the loss of the probes from phagosomes.

The Toronto group suggests that charge-dominated attachment may be reversed downstream of calcium elevation, PS flipping, and PIP2 hydrolysis for a wide range of biological pathways. "If it is happening in other contexts [such as around individual receptor kinases] it would be much harder to tell," says Grinstein, because of the smaller surface areas involved. But Grinstein will be looking next at endocytosis, based on evidence that endosomes and plasma membranes differ in their charge.

Reference:

Yeung, T., et al. 2006. Science. 313:347–351.[Abstract/Free Full Text]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 946K) PPT slides of all figures 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 Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?