Fray, a Drosophila Serine/Threonine Kinase Homologous to Mammalian PASK, Is Required for Axonal Ensheathment

Leiserson, William M.; Harkins, Elizabeth W.; Keshishian, Haig

doi:10.1016/s0896-6273(00)00154-9

Cited by 127 publications

(159 citation statements)

References 38 publications

(3 reference statements)

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“…Like wnk, fray is an essential gene in the fly (55). We therefore knocked down fray in the principal cell of the tubule using the GAL4-UAS system.…”

Section: Resultsmentioning

confidence: 99%

Hypotonicity Stimulates Potassium Flux through the WNK-SPAK/OSR1 Kinase Cascade and the Ncc69 Sodium-Potassium-2-Chloride Cotransporter in the Drosophila Renal Tubule

Schellinger

Huang

et al. 2014

Journal of Biological Chemistry

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“…Like wnk, fray is an essential gene in the fly (55). We therefore knocked down fray in the principal cell of the tubule using the GAL4-UAS system.…”

Section: Resultsmentioning

confidence: 99%

Hypotonicity Stimulates Potassium Flux through the WNK-SPAK/OSR1 Kinase Cascade and the Ncc69 Sodium-Potassium-2-Chloride Cotransporter in the Drosophila Renal Tubule

Schellinger

Huang

et al. 2014

Journal of Biological Chemistry

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“…A BLASTp (Altschul et al 1997) search of the Drosophila genome using human NKCC1 reveals four potential Na 1 -K 1 -Cl À cotransporter genes (Ncc69, CG31547, CG10413, and CG12773). Ncc69 is the most likely NKCC1 homolog as it has significant brain expression (Chintapalli et al 2007) and is known to interact with fray (Leiserson et al 2000), a homolog of the SPAK kinase, which modulates NKCC1 (W. Leiserson and H. Keshishian, personal communication). Here we show that reducing the level of Ncc69 by mutation has only a modest effect on decreasing the BS of kcc DHS1 flies ( Figure 7C).…”

Section: Mb Expression Of Either Drosophila Kccmentioning

confidence: 99%

Seizure Sensitivity Is Ameliorated by Targeted Expression of K+–Cl− Cotransporter Function in the Mushroom Body of the Drosophila Brain

Hekmat-Scafe

Mercado

Fajilan³

et al. 2010

Genetics

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The kcc DHS1 allele of kazachoc (kcc) was identified as a seizure-enhancer mutation exacerbating the bangsensitive (BS) paralytic behavioral phenotypes of several seizure-sensitive Drosophila mutants. On their own, young kcc DHS1 flies also display seizure-like behavior and demonstrate a reduced threshold for seizures induced by electroconvulsive shock. The product of kcc shows substantial homology to KCC2, the mammalian neuronal K transgene was used to determine where cotransporter function is required in order to rescue the kcc DHS1 BS paralytic phenotype. Interestingly, phenotypic rescue is largely accounted for by targeted, circumscribed expression in the mushroom bodies (MBs) and the ellipsoid body (EB) of the central complex. Intriguingly, we observed that MB induction of kcc 1 functioned as a general seizure suppressor in Drosophila. Drosophila MBs have generated considerable interest especially for their role as the neural substrate for olfactory learning and memory; they have not been previously implicated in seizure susceptibility. We show that kcc DHS1 seizure sensitivity in MB neurons acts via a weakening of chemical synaptic inhibition by GABAergic transmission and suggest that this is due to disruption of intracellular Cl À gradients in MB neurons.

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“…The larval nerves exit the ventral nerve cord and innervate the musculature of each individual abdominal segment (Leiserson et al, 2000). As shown in Figure 1J, GFP fluorescence of the repo:GAL4::UAS:GFP third-instar larvae allowed us to visualize the glial cells on the nerve tracts.…”

Section: Axonal Ensheathment Of the Drosophila Embryonic And Larval Pmentioning

confidence: 99%

“…The nerve is surrounded by a neural lamella (Fig. 2, l), which is secreted by the outer glial cells (Leiserson et al, 2000). Within the abdominal nerve, two types of insulations are observed: ensheathment of individual axons by the inner glial membrane and ensheathment of axon fascicles (a group of axons ϭ a fascicle) by the inner glial membrane.…”

Section: Ultrastructural Analysis Of the Axonal Ensheathment And The mentioning

confidence: 99%

Axonal Ensheathment and Septate Junction Formation in the Peripheral Nervous System ofDrosophila

Banerjee¹,

Pillai²,

Paik³

et al. 2006

J. Neurosci.

104

171

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Axonal insulation is critical for efficient action potential propagation and normal functioning of the nervous system. In Drosophila, the underlying basis of nerve ensheathment is the axonal insulation by glial cells and the establishment of septate junctions (SJs) between glial cell membranes. However, the details of the cellular and molecular mechanisms underlying axonal insulation and SJ formation are still obscure. Here, we report the characterization of axonal insulation in the Drosophila peripheral nervous system (PNS). Targeted expression of tau-green fluorescent protein in the glial cells and ultrastructural analysis of the peripheral nerves allowed us to visualize the glial ensheathment of axons. We show that individual or a group of axons are ensheathed by inner glial processes, which in turn are ensheathed by the outer perineurial glial cells. SJs are formed between the inner and outer glial membranes. We also show that Neurexin IV, Contactin, and Neuroglian are coexpressed in the peripheral glial membranes and that these proteins exist as a complex in the Drosophila nervous system. Mutations in neurexin IV, contactin, and neuroglian result in the disruption of blood-nerve barrier function in the PNS, and ultrastructural analyses of the mutant embryonic peripheral nerves show loss of glial SJs. Interestingly, the murine homologs of Neurexin IV, Contactin, and Neuroglian are expressed at the paranodal SJs and play a key role in axon-glial interactions of myelinated axons. Together, our data suggest that the molecular machinery underlying axonal insulation and axon-glial interactions may be conserved across species.

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Fray, a Drosophila Serine/Threonine Kinase Homologous to Mammalian PASK, Is Required for Axonal Ensheathment

Cited by 127 publications

References 38 publications

Hypotonicity Stimulates Potassium Flux through the WNK-SPAK/OSR1 Kinase Cascade and the Ncc69 Sodium-Potassium-2-Chloride Cotransporter in the Drosophila Renal Tubule

Hypotonicity Stimulates Potassium Flux through the WNK-SPAK/OSR1 Kinase Cascade and the Ncc69 Sodium-Potassium-2-Chloride Cotransporter in the Drosophila Renal Tubule

Seizure Sensitivity Is Ameliorated by Targeted Expression of K+–Cl− Cotransporter Function in the Mushroom Body of the Drosophila Brain

Axonal Ensheathment and Septate Junction Formation in the Peripheral Nervous System ofDrosophila

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