A cell-autonomous role for JSAP1 and JLP in mouse cerebellar Purkinje cell survival

We previously reported that the structurally related JNK scaffolding proteins JSAP1 and JLP play functionally redundant and key roles in maintaining mouse cere-bellar Purkinje cell (PC) survival, which may be related to their regulation of axonal transport. The JSAP1 and JLP proteins are also widely expressed in other cell types throughout the brain. Notably, in the cerebellum, JSAP1 is abundantly expressed in the pinceau, a cluster of basket cell (BC) axons and termini that surround the PC axon initial segment. Thus, it is possible that BC-expressed JSAP1 plays a role in PC survival. To investigate this possibility, we generated and analyzed mice containing a PC/BC-specific double knockout (DKO) of Jsap1 and Jlp (Jsap1:Jlp cDKO mice). These mice exhibited PC axonal dystrophy, followed by progressive PC loss, consistent with the phenotypes previously reported for PC-specific Jsap1 and Jlp DKO mice. Furthermore, we found that the phenotypes of Jsap1:Jlp cDKO PCs were rescued by PC-specific transgenic expression of JSAP1. Taken together, these results indicate that BC-expressed JSAP1 plays little or no role in PC survival, and that PC-expressed JSAP1 and JLP play cell-autonomous roles in preventing PC degeneration