Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3)

Kelkar, Nyaya; Delmotte, Marie Hélène; Weston, Claire R.; Barrett, Tamera; Sheppard, Barbara J.; Flavell, Richard A.; Davis, Roger J.

doi:10.1073/pnas.1733944100

Cited by 74 publications

(80 citation statements)

References 27 publications

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“…5), lead us to propose that small syd vesicles may play a role in neurite outgrowth and guidance. This hypothesis is supported by the axonal growth defects observed in syd knock-out animals (17,18). Another link between syd and axonal growth and guidance comes from C. elegans studies.…”

Section: Discussionmentioning

confidence: 82%

“…syd may thus mediate the axonal transport of vesicles, which function as mobile signaling platforms to convey information about axonal injury back to the cell body. In addition, syd-dependent vesicular transport may be critical for axonal growth and regeneration because syd deletion in the central nervous system results in axonal outgrowth defects (17,18). Retrograde injury signals traveling from the injury site back to the cell body are essential to increase the intrinsic growth capacity of neurons following injury and promote successful regeneration (19 -22).…”

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confidence: 99%

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Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

Abe

Almenar-Queralt

Lillo

et al. 2009

Journal of Biological Chemistry

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The extreme polarized morphology of neurons poses a challenging problem for intracellular trafficking pathways. The distant synaptic terminals must communicate via axonal transport with the cell soma for neuronal survival, function, and repair. Multiple classes of organelles transported along axons may establish and maintain the polarized morphology of neurons, as well as control signaling and neuronal responses to extracellular cues such as neurotrophic or stress factors. We reported previously that the motorbinding protein Sunday Driver (syd), also known as JIP3 or JSAP1, links vesicular axonal transport to injury signaling. To better understand syd function in axonal transport and in the response of neurons to injury, we developed a purification strategy based on anti-syd antibodies conjugated to magnetic beads to identify sydassociated axonal vesicles. Electron microscopy analyses revealed two classes of syd-associated vesicles of distinct morphology. To identify the molecular anatomy of syd vesicles, we determined their protein composition by mass spectrometry. Gene Ontology analyses of each vesicle protein content revealed their unique identity and indicated that one class of syd vesicles belongs to the endocytic pathway, whereas another may belong to an anterogradely transported vesicle pool. To validate these findings, we examined the transport and localization of components of syd vesicles within axons of mouse sciatic nerve. Together, our results lead us to propose that endocytic syd vesicles function in part to carry injury signals back to the cell body, whereas anterograde syd vesicles may play a role in axonal outgrowth and guidance.

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Section: Discussionmentioning

confidence: 82%

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confidence: 99%

Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

Abe

Almenar-Queralt

Lillo

et al. 2009

Journal of Biological Chemistry

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“…These phenotypes were distinct from those of JSAP1-null and neural cell-specific Jsap1 − / − (Jsap1 f/f :Nestin-Cre) mice, which die shortly after birth, most likely due to respiratory failure. 18,20 The essential defect leading to this neonatal death is probably in the brainstem rather than the telencephalon, because the brainstem is responsible for the neural network that controls breathing in mammals. Although Jsap1:Jlp cdKO mice were visually indistinguishable from single Jsap1 or Jlp cKO mice at P0, growth retardation became evident during the second postnatal week.…”

Section: Resultsmentioning

confidence: 99%

“…17 Ablating JSAP1 in mice causes various developmental defects in the architecture of the brain, including a lack of telencephalic commissures, whereas no obvious abnormal accumulation of vesicles is observed in the axons. [18][19][20] JLP-null mice are viable and grow normally. 21 On the other hand, JIP1 and JSAP1 were recently shown to be important for the anterograde axonal transport of plasmalemmal precursor vesicles and TrkB, respectively, in rat neurons.…”

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confidence: 99%

JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration

et al. 2015

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Axonal transport is critical for neuronal development and function, and defective axonal transport has been implicated in neurodegenerative diseases. However, how axonal transport is regulated, or how defective transport leads to neuronal degeneration, remains unclear. Here, we report that c-Jun NH 2 -terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3 (JIP3)) and JNK-associated leucine zipper protein (JLP) are essential for postnatal brain development. Mice with a double-knockout (dKO) in Jsap1 and Jlp in the dorsal telencephalon developed progressive neuron loss. Using a primary neuron culture system with induced disruption of targeted genes, combined with gene rescue experiments, we show that JSAP1 and JLP regulate kinesin-1-dependent axonal transport with functional redundancy. We also show that the binding of JSAP1 and JLP to kinesin-1 heavy chain is crucial for interactions between kinesin-1 and microtubules. Furthermore, we describe a molecular mechanism by which defective kinesin-1-dependent axonal transport in Jsap1:Jlp dKO neurons causes axonal degeneration and subsequent neuronal death. JNK hyperactivation because of increased intra-axonal Ca 2+ in the Jsap1:Jlp dKO neurons was found to mediate both the axonal degeneration and neuronal death, in cooperation with the Ca 2+ -dependent protease calpain. Our results indicate that axonal JNK may relocate to the nucleus in a dynein-dependent manner, where it activates the transcription factor c-Jun, resulting in neuronal death. Taken together, our data establish JSAP1 and JLP as positive regulators of kinesin-1-dependent axonal transport, which prevents neuronal degeneration.

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“…In mammals, JIP-3 is required for normal brain development (Kelkar et al, 2003). Recent reports identified the JIP-3 orthologs Sunday driver protein, in Drosophila melanogaster (Bowman et al, 2000), and uncoordinated locomotion UNC-16, in Caenorhabditis elegans (Byrd et al, 2001) as being essential for axonal transport.…”

Section: Discussionmentioning

confidence: 99%

c-Jun NH₂-Terminal Kinase-Interacting Protein-3 Facilitates Phosphorylation and Controls Localization of Amyloid-β Precursor Protein

Muresan¹,

Mureşan²

2005

J. Neurosci.

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Abnormal phosphorylation of amyloid-␤ precursor protein (APP) is a pathologic feature of Alzheimer's disease. To begin to understand the mechanism of APP phosphorylation, we studied this process in differentiating neurons under normal physiological conditions. We found that c-Jun NH 2 -terminal kinase (JNK), not cyclin-dependent kinase 5, is required for APP phosphorylation, leading to localized accumulation of phosphorylated APP (pAPP) in neurites. We show that JNK-interacting protein-3 (JIP-3), a JNK scaffolding protein that does not bind APP, selectively increases APP phosphorylation, accumulation of pAPP into processes, and stimulates process extension in both neurons and COS-1 cells. Downregulation of JIP-3 by small interfering RNA impairs neurite extension and reduces the amount of localized pAPP. Finally, whereas stress-activated JNK generates pAPP only in the cell body, concomitant expression of JIP-3 restores pAPP accumulation into neurites. Thus, APP phosphorylation, transport of the generated pAPP into neurites, and neurite extension are interdependent processes regulated by JIP-3/JNK, in a pathway distinct from stress-activated JNK signaling.

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Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3)

Cited by 74 publications

References 27 publications

Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration

c-Jun NH₂-Terminal Kinase-Interacting Protein-3 Facilitates Phosphorylation and Controls Localization of Amyloid-β Precursor Protein

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Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3)

Cited by 74 publications

References 27 publications

Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration

c-Jun NH2-Terminal Kinase-Interacting Protein-3 Facilitates Phosphorylation and Controls Localization of Amyloid-β Precursor Protein

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c-Jun NH₂-Terminal Kinase-Interacting Protein-3 Facilitates Phosphorylation and Controls Localization of Amyloid-β Precursor Protein