Hexokinases link DJ-1 to the PINK1/parkin pathway

Background

Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer’s disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear.

Methods

We established a cell-based assay to quantify excitotoxicity in primary cultures of mouse hippocampal neurons and investigated the role of tau in exicitotoxicity by modulating neuronal tau expression through genetic ablation or transduction with lentiviral vectors expressing anti-tau shRNA or constructs encoding wildtype versus mutant mouse tau.

Results

We demonstrate that shRNA-mediated knockdown of tau reduces glutamate-induced, NMDA receptor-dependent Ca²⁺ influx and neurotoxicity in neurons from wildtype mice. Conversely, expression of wildtype mouse tau enhances Ca²⁺ influx and excitotoxicity in tau-deficient (Mapt ^−/−) neurons. Reconstituting tau expression in Mapt ^−/− neurons with mutant forms of tau reveals that the tau-related enhancement of Ca²⁺ influx and excitotoxicity depend on the phosphorylation of tau at tyrosine 18 (pY18), which is mediated by the tyrosine kinase Fyn. These effects are most evident at pathologically elevated concentrations of glutamate, do not involve GluN2B–containing NMDA receptors, and do not require binding of Fyn to tau’s major interacting PxxP motif or of tau to microtubules.

Conclusions

Although tau has been implicated in diverse neurological diseases, its most pathogenic forms remain to be defined. Our study suggests that reducing the formation or level of pY18-tau can counteract excitotoxicity by diminishing NMDA receptor-dependent Ca²⁺ influx.

     

Mechanism of Sulfonylurea Herbicide Resistance in the Broadleaf Weed, Kochia scoparia

Selection of kochia (Kochia scoparia) biotypes resistant to the sulfonylurea herbicide chlorsulfuron has occurred through the continued use of this herbicide in monoculture cereal-growing areas in the United States. The apparent sulfonylurea resistance observed in kochia was confirmed in greenhouse tests. Fresh and dry weight accumulation in the resistant kochia was 2- to >350-fold higher in the presence of four sulfonylurea herbicides as compared to the susceptible biotype. Acetolactate synthase (ALS) activity isolated from sulfonylurea-resistant kochia was less sensitive to inhibition by three classes of ALS-inhibiting herbicides, sulfonylureas, imidazolinones, and sulfonanilides. The decrease in ALS sensitivity to inhibition (as measured by the ratio of resistant I₅₀ to susceptible I₅₀) was 5- to 28-fold, 2- to 6-fold, and 20-fold for sulfonylurea herbicides, imidazolinone herbicides, and a sulfonanilide herbicide, respectively. No differences were observed in the ALS-specific activities or the rates of [¹⁴C]chlorsulfuron uptake, translocation, and metabolism between susceptible and resistant kochia biotypes. The K_m values for pyruvate using ALS from susceptible and resistant kochia were 2.13 and 1.74 mm, respectively. Based on these results, the mechanism of sulfonylurea resistance in this kochia biotype is due solely to a less sulfonylurea-sensitive ALS enzyme.     

Monitoring of pollen rain in moss polsters and mats in view of their suitability as controls for determining the air-borne component of pollen spectra in herbivore faeces

Pollen has been extracted from six bryophyte and two lichen taxa, sampled from three habitats: upland heath, lowland bog and mixed woodland, in both west and east Scotland. The highest number of pollen taxa was recorded in bothSphagnum andThuidium; the lowest numbers of pollen taxa were recorded in two of the mosses and both lichens. For pollen rain control purposes in herbivore faecal studies, woodland species of bryophytes are not suitable due to the sheltering effects from rain provided by the overhead canopy. Open habitats such as moorland heath and bog provide polsters/mats which normally trap pollen rain more effectively for control purposes. The aim of this study was twofold: to observe the effectiveness of selected polsters and lichens as traps for pollen rain and to establish eventually, whether or not such vegetative traps could be used as controls in pollen spectra analyses of herbivore faeces for the determination of nutritional regime and habitat. From a comparison with recent studies in north west Spain of three taxa in common with Scottish samples,Polytrichum demonstrated a consistently higher number of pollen taxa trapped.Thuidium andCladonia all yielded between one and a half and three times the number of pollen taxa as in the same three bryophyte/lichen taxa sampled in Scotland. Investigation relating the pollen rain trapped in polsters to that in faecal material are continuing, and will be reported in due course. This paper is based on one given by E.C. at the 5th International Aerobiology Conference, held at Bangalore, India, August 1994.     

Monitoring of pollen rain in moss polsters and mats in view of their suitability as controls for determining the air-borne component of pollen spectra in herbivore faeces

Pollen has been extracted from six bryophyte and two lichen taxa, sampled from three habitats: upland heath, lowland bog and mixed woodland, in both west and east Scotland. The highest number of pollen taxa was recorded in bothSphagnum andThuidium; the lowest numbers of pollen taxa were recorded in two of the mosses and both lichens. For pollen rain control purposes in herbivore faecal studies, woodland species of bryophytes are not suitable due to the sheltering effects from rain provided by the overhead canopy. Open habitats such as moorland heath and bog provide polsters/mats which normally trap pollen rain more effectively for control purposes. The aim of this study was twofold: to observe the effectiveness of selected polsters and lichens as traps for pollen rain and to establish eventually, whether or not such vegetative traps could be used as controls in pollen spectra analyses of herbivore faeces for the determination of nutritional regime and habitat. From a comparison with recent studies in north west Spain of three taxa in common with Scottish samples,Polytrichum demonstrated a consistently higher number of pollen taxa trapped.Thuidium andCladonia all yielded between one and a half and three times the number of pollen taxa as in the same three bryophyte/lichen taxa sampled in Scotland. Investigation relating the pollen rain trapped in polsters to that in faecal material are continuing, and will be reported in due course.This paper is based on one given by E.C. at the 5th International Aerobiology Conference, held at Bangalore, India, August 1994.