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We are investigating changes in cytoskeletal protein dynamics underlying the effects of soluble growth factors on neurons. Of particular interest is the signaling role Ca plays in such processes. |
We have discovered that 5-HT (serotonin) treatment activates IP3 dependent Ca release from intracellular stores, resulting in ~20% increase in baseline Ca levels. This in turn leads to activation of the actin severing protein cofilin which increases the rate of retrograde actin network flow in the growth cone and faster rates of neurite outgrowth. We are currently investigating the necessary role non-muscle myosin II plays in this process. |
| Endoplasmic Reticulum distribution | |
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| Ca2+ is released from intracellular ER stores (green) that penetrate the peripheral growth cone domain. |
ER is tranported into the peripheral domain of the growth cone as cargo on dynamic microtubules. |
| Ca increase in response to 5-HT treatment | Correlating structure, Ca levels and actin dynamics |
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| For details see: http://forscherlab.yale.edu/publications/calcineurin-dependent-cofilin-a… |