Palmitoylation couples the kinases DLK and JNK3 to facilitate prodegenerative axon-to-soma signaling

• DOI: 10.1126/scisignal.abh2674
• Publication Date: 2022-03-29T17:56:33Z
• Authors: Jingwen Niu; Sabrina M. Holland; Andrea Ketschek; Kaitlin M. Collura; Natasha L. Hesketh; Takashi Hayashi; Gianluca Gallo; Gareth M. Thomas
• Keywords: Palmitoylation

Dual leucine-zipper kinase (DLK; a MAP3K) mediates neuronal responses to diverse injuries and insults through the c-Jun N-terminal (JNK) family of mitogen-activated protein kinases (MAPKs). Here, we identified two ways which DLK is coupled neural-specific isoform JNK3 control prodegenerative signaling. catalyzed positive feedback phosphorylation that further activated locked DLK-JNK3 module in highly active state. Neither homologous MAP3Ks nor MAPK could support this loop. Unlike related JNK1 JNK2 promote axon-to-soma signaling were endogenously palmitoylated. Moreover, palmitoylation targeted both same axonal vesicles, was essential for retrograde response optic nerve crush injury vivo. These findings provide previously unappreciated insights into DLK-JNK relevant neuropathological conditions answer long-standing questions regarding selective roles JNK3.