“No gain, no pain: phosphoinositide regulation of TRPV1 ion channels”
Host: Jianmin Cui (WashU Biomedical Engineering)
Abstract: The sensitivity of peripheral pain-receptor neurons to noxious thermal and chemical stimuli is tuned by a variety of receptors and second messengers, in part through tuning the sensitivity and number of TRPV1 ion channels that act as receptors for thermal and chemical stimuli. The gain can be decreased, producing desensitization, or increased, producing hyperalgesia. Over the last decade, significant progress has been made in understanding both desensitization and hyperalgesia at the cellular and molecular levels. This talk will focus on the roles of phosphoinositide lipids in desensitization and hyperalgesia. The phosphoinositide PI(4,5)P2 acts as a co-factor for TRPV1 ion channels. Channel activity decreases PI(4,5)P2 levels in a negative feedback loop that in turn decreases channel activity. In contrast, the phosphoinositide lipid PI(3,4,5)P3 is part of a growth factor stimulated signaling cascade that increases the number of TRPV1 ion channels in the neuronal plasma membrane. The increased number of channels make the cell more sensitive to noxious TRPV1 activators. Our most recent work shows that TRPV1 potentiates the activity of the PI(3,4,5)P3-generating lipid kinase PI3K in response to growth factor. A fragment corresponding to the N-terminal region of TRPV1 is sufficient to produce the potentiation, suggesting that potentiation may involve an increase in the catalytic activity of PI3K. We are currently examining whether potentiation of PI3K is conserved among members of the TRPV family of ion channels.
For inquiries contact Karen Teasdale.
GETTING TO CAMPUS
Please know that there have been changes to parking on the Danforth Campus due to the east end construction.
Metrolink or biking to the Danforth campus are the easiest options.
If you choose to drive, the closest parking is in Millbrook garage off of Forest Park Parkway and Throop Drive. It will take approx. 15 minutes to walk to our building.