title: Critical role of JSAP1 and JLP in axonal transport in the cerebellar Purkinje cells of mice.
abstract: 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.
authors: Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors: Tokiharu
authors: T
authors: Sato
authors: Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors: Momoe
authors: M
authors: Ishikawa
authors: Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan.
authors: Toru
authors: T
authors: Yoshihara
authors: Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors: Ryota
authors: R
authors: Nakazato
authors: Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan.
authors: Haruhiro
authors: H
authors: Higashida
authors: Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan.
authors: Masahide
authors: M
authors: Asano
authors: Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. Electronic address: katsuji@staff.kanazawa-u.ac.jp.
authors: Katsuji
authors: K
authors: Yoshioka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D002531:Cerebellum / Q000166:cytology*; D055786:Gene Knockout Techniques; D016547:Kinesins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C403619:Mapk8ip3 protein, mouse; D009419:Nerve Tissue Proteins; C468928:Spag9 protein, mouse; D016547:Kinesins
keywords: Autophagy; Axonal swelling; Kinesin-1; Neurodegeneration; Ubiquitin