Fig. 2.

Summary of Molecular Effects Induced in Neuronal Precursor Cells by the Cytotoxic Drug Paclitaxel

Binding of paclitaxel to NCS-1 stabilizes the Ca²⁺-bound conformation of this protein and thus causes an increased binding of NCS-1 to the InsP₃R. As a result, the InsP₃R is positively modulated, and an increased release of Ca²⁺ from the endoplasmic reticulum to the cytoplasm occurs. Ca²⁺ in turn, among other cellular processes, activates the Ca²⁺-dependent protease µ-calpain, which not only degrades NCS-1 in a negative feedback loop, but is also able to trigger a number of molecular pathways, including apoptosis. Interaction of NCS-1 with the InsP₃R can be inhibited with lithium ions. Ca²⁺ indicates calcium; InsP₃R, inositol-1,4,5-trisphosphate-receptor; NCS-1, neuronal calcium sensor 1-protein; PTX, paclitaxel. Figure adapted from Huehnchen et al.⁵⁶