APLIP1, a Kinesin Binding JIP-1/JNK Scaffold Protein, Influences the Axonal Transport of Both Vesicles and Mitochondria in Drosophila

Horiuchi, Dai; Barkus, Rosemarie V.; Pilling, Aaron D.; Gassman, Andrew; Saxton, William M.

doi:10.1016/j.cub.2005.10.047

Cited by 134 publications

(132 citation statements)

References 23 publications

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“…Both JIP1 and JIP2 strongly potentiate JNK activation by the MLK family, but little evidence supports participation in signaling by the MEKK group of MAP3Ks. APLIP1, a neuronally expressed D. melanogaster homolog of JIP1, was identified in a genetic screen for kinesin heavy chaininteracting proteins, perhaps consistent with earlier studies suggesting that JIPs may move JNKs along axons to growth cones (Kelkar et al, 2000;Horiuchi et al, 2005).…”

Section: Structural Insights and Regulation Via Docking Domainssupporting

confidence: 79%

Differential regulation and properties of MAPKs

2007

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Mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs including embryogenesis, proliferation, differentiation and apoptosis based on cues derived from the cell surface and the metabolic state and environment of the cell. In mammals, there are more than a dozen MAPK genes. The best known are the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK(1-3)) and p38(a, b, c and d) families. ERK3, ERK5 and ERK7 are other MAPKs that have distinct regulation and functions. MAPK cascades consist of a core of three protein kinases. Despite the apparently simple architecture of this pathway, these enzymes are capable of responding to a bewildering number of stimuli to produce exquisitely specific cellular outcomes. These responses depend on the kinetics of their activation and inactivation, the subcellular localization of the kinases, the complexes in which they act, and the availability of substrates. Fine-tuning of cascade activity can occur through modulatory inputs to cascade component from the primary kinases to the scaffolding accessory proteins. Here, we describe some of the properties of the three major MAPK pathways and discuss how these properties govern pathway regulation and activity.

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Section: Structural Insights and Regulation Via Docking Domainssupporting

confidence: 79%

Differential regulation and properties of MAPKs

2007

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“…However, abnormal neuritogenesis of jip1 Ϫ/Ϫ neurons may not simply be a consequence of altered JNK signaling. JIP1 was shown to interact with kinesin-1 and doublecortin, thereby regulating polarization, transport, and axon outgrowth of cortical neurons (Gdalyahu et al, 2004;Horiuchi et al, 2005;Dajas-Bailador et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Distinct Roles of c-Jun N-Terminal Kinase Isoforms in Neurite Initiation and Elongation during Axonal Regeneration

Barnat¹,

Enslen²,

Propst³

et al. 2010

Journal of Neuroscience

106

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c-Jun N-terminal kinases (JNKs) (comprising JNK1-3 isoforms) are members of the MAPK (mitogen-activated protein kinase) family, activated in response to various stimuli including growth factors and inflammatory cytokines. Their activation is facilitated by scaffold proteins, notably JNK-interacting protein-1 (JIP1). Originally considered to be mediators of neuronal degeneration in response to stress and injury, recent studies support a role of JNKs in early stages of neurite outgrowth, including adult axonal regeneration. However, the function of individual JNK isoforms, and their potential effector molecules, remained unknown. Here, we analyzed the role of JNK signaling during axonal regeneration from adult mouse dorsal root ganglion (DRG) neurons, combining pharmacological JNK inhibition and mice deficient for each JNK isoform and for JIP1. We demonstrate that neuritogenesis is delayed by lack of JNK2 and JNK3, but not JNK1. JNK signaling is further required for sustained neurite elongation, as pharmacological JNK inhibition resulted in massive neurite retraction. This function relies on JNK1 and JNK2. Neurite regeneration of jip1 Ϫ/Ϫ DRG neurons is affected at both initiation and extension stages. Interestingly, activated JNKs (phospho-JNKs), as well as JIP1, are also present in the cytoplasm of sprouting or regenerating axons, suggesting a local action on cytoskeleton proteins. Indeed, we have shown that JNK1 and JNK2 regulate the phosphorylation state of microtubule-associated protein MAP1B, whose role in axonal regeneration was previously characterized. Moreover, lack of MAP1B prevents neurite retraction induced by JNK inhibition. Thus, signaling by individual JNKs is differentially implicated in the reorganization of the cytoskeleton, and neurite regeneration.

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“…The anti-HA monoclonal antibody 16B12 (1:200 dilution; Covance) and anti-mouse Alexa 568 (1:200 dilution; Molecular Probes) were used for staining. UAS-mSpitz-GFP (a gift from Ben-Zion Shilo) was used as a microsomal marker (19). The anti-mouse ␤-actin monoclonal antibody C4 (1:50,000 dilution; Santa Cruz Biotechnology, Inc., Santa Cruz, CA) was used for Western blotting.…”

Section: Derivatization Of Steroids and Hplc-electrospray Ionization mentioning

confidence: 99%

The Conserved Rieske Oxygenase DAF-36/Neverland Is a Novel Cholesterol-metabolizing Enzyme

Yoshiyama-Yanagawa

Enya

Shimada-Niwa

et al. 2011

Journal of Biological Chemistry

150

118

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Steroid hormones play essential roles in a wide variety of biological processes in multicellular organisms. The principal steroid hormones in nematodes and arthropods are dafachronic acids and ecdysteroids, respectively, both of which are synthesized from cholesterol as an indispensable precursor. The first critical catalytic step in the biosynthesis of these ecdysozoan steroids is the conversion of cholesterol to 7-dehydrocholesterol. However, the enzymes responsible for cholesterol 7,8-dehydrogenation remain unclear at the molecular level. Here we report that the Rieske oxygenase DAF-36/Neverland (Nvd) is a cholesterol 7,8-dehydrogenase. The daf-36/nvd genes are evolutionarily conserved, not only in nematodes and insects but also in deuterostome species that do not produce dafachronic acids or ecdysteroids, including the sea urchin Hemicentrotus pulcherrimus, the sea squirt Ciona intestinalis, the fish Danio rerio, and the frog Xenopus laevis. An in vitro enzymatic assay system reveals that all DAF-36/Nvd proteins cloned so far have the ability to convert cholesterol to 7-dehydrocholesterol. Moreover, the lethality of loss of nvd function in the fruit fly Drosophila melanogaster is rescued by the expression of daf-36/ nvd genes from the nematode Caenorhabditis elegans, the insect Bombyx mori, or the vertebrates D. rerio and X. laevis. These data suggest that daf-36/nvd genes are functionally orthologous across the bilaterian phylogeny. We propose that the daf-36/nvd family of proteins is a novel conserved player in cholesterol metabolism across the animal phyla.Steroid hormones are crucial for development, growth, and homeostasis in multicellular organisms. Cholesterol and other sterol(s) serve as indispensable precursors for the biosynthesis of steroid hormones, and the conversion of cholesterol to the next specific intermediate is a crucial biochemical step across species (1-4). In the biosynthesis of vertebrate steroid hormones, cholesterol is commonly converted to pregnenolone by side-chain cleavage catalyzed by the cytochrome P450 monooxygenase P450scc/CYP11A1 (2). The step catalyzed by CYP11A1 is the key rate-limiting step in the synthesis of all vertebrate steroids, and it thus is controlled by numerous physiological responses throughout the life cycle (2, 5).Cholesterol is also required for steroid hormone biosynthesis in protostomes, including nematodes and arthropods (1, 6). However, the molecular mechanisms of cholesterol metabolism in these ecdysozoan animals have not been fully elucidated. The principal steroid hormones in nematodes and arthropods are dafachronic acids and ecdysteroids, respectively, both of which play pivotal roles in the regulation of developmental timing, reproduction, and longevity (1,7,8). In the biosynthesis of both dafachronic acids and ecdysteroids, which is different from the biosynthesis of vertebrate steroid hormones, cholesterol is converted to 7-dehydrocholesterol (7dC) 5 by dehydrogenation of the carbons at positions 7 and 8 (Fig. 1A) (9). Nematodes and arthropods lo...

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APLIP1, a Kinesin Binding JIP-1/JNK Scaffold Protein, Influences the Axonal Transport of Both Vesicles and Mitochondria in Drosophila

Cited by 134 publications

References 23 publications

Differential regulation and properties of MAPKs

Differential regulation and properties of MAPKs

Distinct Roles of c-Jun N-Terminal Kinase Isoforms in Neurite Initiation and Elongation during Axonal Regeneration

The Conserved Rieske Oxygenase DAF-36/Neverland Is a Novel Cholesterol-metabolizing Enzyme

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