Premium
Critical role of JSAP1 and JLP in axonal transport in the cerebellar Purkinje cells of mice
Author(s) -
Sato Tokiharu,
Ishikawa Momoe,
Yoshihara Toru,
Nakazato Ryota,
Higashida Haruhiro,
Asano Masahide,
Yoshioka Katsuji
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.08.024
Subject(s) - microbiology and biotechnology , kinesin , cerebellum , purkinje cell , scaffold protein , autophagy , biology , kinase , leucine zipper , protein kinase a , axoplasmic transport , chemistry , neuroscience , signal transduction , biochemistry , microtubule , transcription factor , apoptosis , gene
JNK/stress‐activated protein kinase‐associated protein 1 (JSAP1) and JNK‐associated leucine zipper protein (JLP) are structurally related scaffolding proteins that are highly expressed in the brain. Here, we found that JSAP1 and JLP play functionally redundant and essential roles in mouse cerebellar Purkinje cell (PC) survival. Mice containing PCs with deletions in both JSAP1 and JLP exhibited PC axonal dystrophy, followed by gradual, progressive neuronal loss. Kinesin‐1 cargoes accumulated selectively in the swollen axons of Jsap1 / Jlp ‐deficient PCs. In addition, autophagy inactivation in these mice markedly accelerated PC degeneration. These findings suggest that JSAP1 and JLP play critical roles in kinesin‐1‐dependent axonal transport, which prevents brain neuronal degeneration.