Scaffold protein JSAP1 is transported to growth cones of neurites independent of JNK signaling pathways in PC12h cells

The c-Jun NH₂-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 [JSAP1; also known as JNK-interacting protein 3 (JIP3)] has been identified as a scaffold protein for JNK mitogen-activated protein kinase signal transduction pathways and as a cargo adapter in the conventional kinesin-mediated transport system. Furthermore, a functional relationship between UNC-16, the C. elegans ortholog of JSAP1, and JNK signaling has been established genetically. In this study, we first demonstrated that the kinesin light chain is required for the targeting and localization of JSAP1 to the tips of neurites in PC12h cells. Furthermore, to understand whether JNK signaling is involved in kinesin-mediated JSAP1 trafficking, we established stable PC12h cell lines that expressed wild-type JSAP1 or its mutant lacking the JNK-binding domain (JBD). Immunocytochemical studies of the cell lines indicated that the mutant JSAP1 was localized to the growth cones of differentiating PC12h cells in a similar manner to wild-type JSAP1. Taken together, these results suggest that the proper subcellular localization of JSAP1 along microtubules probably does not require JNK signaling.