Microtubule dynamics at the growth cone are mediated by ?7 nicotinic receptor activation of a G?q and IP3 receptor pathway.

ABSTRACT: The ?7 nicotinic receptor (?7) plays an important role in neuronal growth and structural plasticity in the developing brain. We have recently characterized a G-protein-signaling pathway regulated by ?7 that directs the growth of neurites in developing neural cells. Now we show that choline activation of ?7 promotes a rise in intracellular calcium from local ER stores via G?q signaling, leading to IP3 receptor (IP3R) activation at the growth cone of differentiating PC12 cells. A mutant ?7 significantly attenuated in calcium conductance (D44A; P<0.001) was found to be unable to promote IP3R signaling and calcium store release. In addition, calcium elevation via ?7 correlates with a significant attenuation in the rate of microtubule invasion of the growth cone (P<0.001). This process was also attenuated in the D44A mutant and blocked by an inhibitor of the IP3R, suggesting that calcium flow through the ?7 channel and activation of the G?q pathway are necessary for growth. Taken together, the findings reveal an inhibitory mechanism of ?7 on cytoskeletal growth via the intracellular calcium activity of the receptor channel and the G?q signaling pathway at the growth cone.-Nordman, J. C., Kabbani, N. Microtubule dynamics at the growth cone are mediated by ?7 nicotinic receptor activation of a G?q and IP3 receptor pathway.

SUBMITTER: Nordman JC 

PROVIDER: S-EPMC4062821 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other