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Channels rush in

Growth factors recruit TRPC5 channels to the membrane. Clapham/Macmillan

Channels lurking in vesicles just beneath the cell surface can leap into action by inserting into the plasma membrane, say Vassilios Bezzerides, David Clapham (Harvard Medical School, Boston, MA), and colleagues. The resulting increase in Ca²⁺ current slows down and perhaps changes the outgrowth direction of advancing neurites.

The Boston group saw TRPC5 Ca²⁺ channels transferring into the plasma membrane, as measured by total internal reflection microscopy, electrophysiology, and surface biotinylation, in response to several growth factors. "Instead of controlling just gating, you are controlling availability," says Clapham.

Recruitment and activation of TRPC5 Ca²⁺ currents were dependent on activated Rac and production of PIP₂. In combination with previous work, this suggests the following scenario: activated growth factor receptors turn on PI3K-mediated production of PIP₃; PIP₃ recruits an exchange factor for Rac; and active Rac binds a kinase that produces PIP₂. The binding target for PIP₂ may be synaptotagmin, which colocalizes with TRPC5 in vesicles.

The recruitment is transient, thus helping the cell to avoid flooding its narrow neurites with too much calcium. The calcium admitted by TRPC5 slows down neurites, possibly so they can respond to turning cues. Clapham now wants to see whether such "just in time" channel insertion events are a generalized feature of TRP channel regulation.

Reference:

Bezzerides, V.J., et al. 2004. Nat. Cell Biol. doi:10.1038/ncb1150.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 762K) 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?