Diverse Roles of JNK and MKK Pathways in the Brain
Figure 3
The JNK signaling pathway regulates axonal transport and autophagy. (a) Model of how the JNK signaling pathway controls axonal transport in Drosophila. Axonal transport is driven along MT by kinesin-1, which binds to the vesicles that make up its cargo through APLIP1 (Drosophila JIP1) and APPL (APP). This process is driven by Wnd (DLK), which is activated by unknown upstream signals, and phosphorylates Hep (MKK7). Activated Hep then phosphorylates and activates Bsk (JNK), which then directly or indirectly modifies the linkage complex and causes APLIP1 and the cargo to dissociate from kinesin-1. (This figure is excerpted from [39] with some modifications.) (b) Model of the regulation of neuronal autophagy in mice. In normal neurons, constitutively activated JNKs suppress CDK-induced FoxO1 activation, preventing autophagy. When all three of JNK1, JNK2, and JNK3 are disrupted, CDK-mediated FoxO1 activation increases Bnip3 expression. High levels of Bnip inhibit the binding of Beclin1 to Bcl2, and this freshly released Beclin1 induces autophagy.
