title: Isoform-specific palmitoylation of JNK regulates axonal development.
abstract: The c-jun N-terminal kinase (JNK) proteins are encoded by three genes (Jnk1-3), giving rise to 10 isoforms in the mammalian brain. The differential roles of JNK isoforms in neuronal cell death and development have been noticed in several pathological and physiological contexts. However, the mechanisms underlying the regulation of different JNK isoforms to fulfill their specific roles are poorly understood. Here, we report an isoform-specific regulation of JNK3 by palmitoylation, a posttranslational modification, and the involvement of JNK3 palmitoylation in axonal development and morphogenesis. Two cysteine residues at the COOH-terminus of JNK3 are required for dynamic palmitoylation, which regulates JNK3's distribution on the actin cytoskeleton. Expression of palmitoylation-deficient JNK3 increases axonal branching and the motility of axonal filopodia in cultured hippocampal neurons. The Wnt family member Wnt7a, a known modulator of axonal branching and remodelling, regulates the palmitoylation and distribution of JNK3. Palmitoylation-deficient JNK3 mimics the effect of Wnt7a application on axonal branching, whereas constitutively palmitoylated JNK3 results in reduced axonal branches and blocked Wnt7a induction. Our results demonstrate that protein palmitoylation is a novel mechanism for isoform-specific regulation of JNK3 and suggests a potential role of JNK3 palmitoylation in modulating axonal branching.
authors.affiliation: College of Interdisciplinary Studies, University of British Columbia, Brain Research Centre, 2211 Wesbrook Mall, Vancouver, BC V6T2B5, Canada. photonyg@interchange.ubc.ca
authors.forename: G
authors.initials: G
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Yang
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.forename: A
authors.initials: A
authors.lastname: Coquinco
authors.forename: W
authors.initials: W
authors.lastname: Wen
authors.forename: L
authors.initials: L
authors.lastname: Kojic
authors.forename: W
authors.initials: W
authors.lastname: Jia
authors.forename: M
authors.initials: M
authors.lastname: Cynader
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000201:enzymology*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D054878:Lipoylation / Q000502:physiology*; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C490507:Wnt7a protein, rat; D048057:Mitogen-Activated Protein Kinase 10