c-Jun NH2-terminal Kinase (JNK)-interacting Protein-3 (JIP3) Regulates Neuronal Axon Elongation in a Kinesin- and JNK-dependent Manner

Sun, Tao; Yu, Naisen; Zhai, Lu-Kai; Li, Na; Zhang, Chao; Zhou, Liang; Huang, Zhuo; Jiang, Xingyu; Shen, Ying; Chen, Zhe-Yu

doi:10.1074/jbc.m113.464453

Cited by 55 publications

(64 citation statements)

References 60 publications

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“…In ULK4 knockdown cells, we observed a significant reduction in the phosphorylation of ERK1/2 (P50.001, n53) and p38 MAPKs (P50.003, n53). Upregulated activity of the stress-activated c-Jun N-terminal kinases (JNKs) is highly involved in neuritogenesis, including axon formation, polarization, extension, synaptic plasticity, and dendrite development during brain development or under a stress challenge (Coffey et al, 2000;Rosso et al, 2005;Oliva et al, 2006;Barnat et al, 2010;Qu, et al, 2013;Sun et al, 2013). In line with these reports, we observed consistently decreased expression of phosphorylated JNK in ULK4 knockdown cells (P50.008, n53; Fig.…”

Section: Ulk4 Modulates Erk P38 Mapk Pkc and Jnk Pathwayssupporting

confidence: 79%

“…Jnk1 2/2 mice exhibit disrupted anterior commissure tract formation and abnormal axonal microtubule integrity (Chang et al, 2003), as well as altered dendritic architecture (Björkblom et al, 2005). In addition, JNKinteracting protein 3 also promotes axon elongation in a JNKdependent manner through facilitating actin polymerization (Sun et al, 2013). In the present study, the CNV frequency of MAPK8-10 was comparable in the ISC cases and controls, with one MAPK8 duplication plus one MAPK9 partial duplication in the ISC cases, and one MAPK9 plus one MAPK10 partial duplication in the controls.…”

Section: Discussionsupporting

confidence: 51%

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Recurrent deletions of ULK4 in schizophrenia: a novel gene crucial for neuritogenesis and neuronal motility

Luo

Hunter

et al. 2013

Journal of Cell Science

115

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Although many pathogenic copy number variations (CNVs) are associated with neuropsychiatric diseases, few of them have been functionally characterised. Here we report multiple schizophrenia cases with CNV abnormalities specific to unc-51-like kinase 4 (ULK4), a serine/threonine kinase gene. Deletions spanning exons 21-34 of ULK4 were present in 4 out of 3391 schizophrenia patients from the International Schizophrenia Consortium, but absent in 3181 controls. Deletions removing exons 33 and 34 of the large splice variant of ULK4 also were enriched in Icelandic schizophrenia and bipolar patients compared with 98,022 controls (P50.0007 for schizophrenia plus bipolar disorder). Combining the two cohorts gives a P-value less than 0.0001 for schizophrenia, or for schizophrenia plus bipolar disorder. The expression of ULK4 is neuron-specific and developmentally regulated. ULK4 modulates multiple signalling pathways that include ERK, p38, PKC and JNK, which are involved in stress responses and implicated in schizophrenia. Knockdown of ULK4 disrupts the composition of microtubules and compromises neuritogenesis and cell motility. Targeted Ulk4 deletion causes corpus callosum agenesis in mice. Our findings indicate that ULK4 is a rare susceptibility gene for schizophrenia.

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Section: Ulk4 Modulates Erk P38 Mapk Pkc and Jnk Pathwayssupporting

confidence: 79%

Section: Discussionsupporting

confidence: 51%

Recurrent deletions of ULK4 in schizophrenia: a novel gene crucial for neuritogenesis and neuronal motility

Luo

Hunter

et al. 2013

Journal of Cell Science

115

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“…UNC-16 (JIP3) is also known to regulate axon elongation and branching as well as axonal transport and regeneration after injury (Cavalli et al 2005;Bilimoria et al 2010;Suzuki et al 2010;Sun et al 2013;Nix et al 2014;Watt et al 2015). However, it is unknown whether these axon growth functions of SAD-1 and UNC-16 are related and whether other CSS system proteins also participate.…”

Section: )mentioning

confidence: 99%

“…Indeed, there is genetic evidence in mice that JIP3 can function as an adaptor that promotes the Kinesin-1-mediated transport of TrkB receptors as well as one or more unidentified cargos relevant to axon elongation and neuronal degeneration (Huang et al 2011;Sun et al 2013;Sato et al 2015;Watt et al 2015).…”

mentioning

confidence: 99%

UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons

Edwards¹,

Morrison²,

Yorks³

et al. 2015

Genetics

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The conserved protein UNC-16 (JIP3) inhibits the active transport of some cell soma organelles, such as lysosomes, early endosomes, and Golgi, to the synaptic region of axons. However, little is known about UNC-16's organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an unc-16 suppressor screen in Caenorhabditis elegans to discover that UNC-16 acts through CDK-5 (Cdk5) and two conserved synapse assembly proteins: SAD-1 (SAD-A Kinase), and SYD-2 (Liprin-a). Genetic analysis of all combinations of double and triple mutants in unc-16(+) and unc-16(2) backgrounds showed that the three proteins (CDK-5, SAD-1, and SYD-2) are all part of the same organelle transport regulatory system, which we named the CSS system based on its founder proteins. Further genetic analysis revealed roles for SYD-1 (another synapse assembly protein) and STRADa (a SAD-1-interacting protein) in the CSS system. In an unc-16(2) background, loss of the CSS system improved the sluggish locomotion of unc-16 mutants, inhibited axonal lysosome accumulation, and led to the dynein-dependent accumulation of lysosomes in dendrites. Time-lapse imaging of lysosomes in CSS system mutants in unc-16(+) and unc-16(2) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. UNC-16 also uses the CSS system to regulate the distribution of early endosomes in neurons and, to a lesser extent, Golgi. The data reveal a new and unprecedented role for synapse assembly proteins, acting as part of the newly defined CSS system, in mediating UNC-16's organelle transport regulatory function.KEYWORDS Caenorhabditis elegans; axonal transport; JIP3; Cdk5; Liprin; SAD-A; dynein N EURONS have a unique architecture consisting of a cell soma, one or more dendrites that receive information, and a single axon, which can be a single process or intricately branched. Part of the axon is specialized to form synapses, which integrate and transmit information to other neurons or muscle cells via synaptic vesicles and dense core vesicles. This unique architecture and cell biology places extraordinary demands on the membrane-trafficking and transport machinery. In addition to transporting synaptic vesicles and dense core vesicles long distances into axons, motor neurons must also restrict, or even prevent, the flow of some organelles, including Golgi, lysosomes, and endosomes, into the synaptic region of their axons, which, under normal conditions, are relatively devoid of these organelles compared to cell somas. However, there may be special conditions, such as the need for axon repair or growth, where neurons require cell soma organelles in their axons, so the regulatory system for organelle transport must include components that inhibit, as well as promote, axonal transport. The association of mutations in the axonal transport machinery with neurodegenerative disorders in mice and humans underscores the importance of a properly functioning transport system for the long-term viab...

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“…Сүн нар [17] болон Ватт нар [18] JSAP нь мотор уургийн идэвх ба хөдөлгөөнийг зохицуулдаг болохыг харуулсан [13][14][15][16][17][18]. Мэдрэлийн эсийн аксоны уртсах, салаалах, мэдрэлийн ширхэг үүсэхэд ч JSAP уургууд чухал үүрэгтэй ажээ [19][20][21][22]. Түүнчлэн эсийн митоз хуваагдлын прометафаз үе болон цитокинезийн үед JSAP уургууд чухал үүрэгтэй болох нь тогтоогдоод байна [23,24].…”

Section: оршилunclassified

Хавдар Эсийн Үйл Ажиллагаанд Jsap (Jnk/Stress-Activated Protein Kinase-Associated Protein) Уургийн Оролцоо

Erdenebaatar¹,

Риота²,

Кацүжи³

2016

Proc. Mong. Acad. Sci.

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c-Jun NH2-terminal Kinase (JNK)-interacting Protein-3 (JIP3) Regulates Neuronal Axon Elongation in a Kinesin- and JNK-dependent Manner

Cited by 55 publications

References 60 publications

Recurrent deletions of ULK4 in schizophrenia: a novel gene crucial for neuritogenesis and neuronal motility

Recurrent deletions of ULK4 in schizophrenia: a novel gene crucial for neuritogenesis and neuronal motility

UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons

Хавдар Эсийн Үйл Ажиллагаанд Jsap (Jnk/Stress-Activated Protein Kinase-Associated Protein) Уургийн Оролцоо

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