Phosphoglycerate kinase is a central leverage point in Parkinson’s Disease driven neuronal metabolic deficits
By Emma Sherrell onPreprint: The data indicates that nerve terminal bioenergetic deficits may underly a spectrum of PD susceptibilities and the identification of PGK1 as the limiting enzyme in axonal glycolysis provides a mechanistic underpinning for therapeutic protection.
Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production
By Emma Sherrell onPreprint: The authors'results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.
M4-mediated cholinergic transmission is reduced in Parkinsonian mice and its restoration alleviates motor deficits and levodopa-induced dyskinesia
By Emma Sherrell onPreprint: Despite M4-receptors being thought to mediate anti-kinetic effects, restoring M4-receptor function partially rescued Parkinsonian balance and coordination deficits and limited the development of levodopa-induced dyskinetic behaviors, indicating that decreased M4-function contributed to circuit and motor dysfunctions in response to DA loss.
Adaptor protein-3 produces synaptic vesicles that release phasic dopamine
By Emma Sherrell onThe burst firing of midbrain dopamine neurons releases a phasic dopamine signal that mediates reinforcement learning. AP-3 and VPS41 promote the axonal polarity of dopamine release but enable learning by producing a distinct population of SVs tuned specifically to high firing frequency that confers the phasic release of dopamine.
Next-generation sequencing of AAV.CAP-Mac enrichment from Chuapoco et al. (2023)
By Emma Sherrell onDataset of next-generation sequencing of enrichment of AAV.CAP-Mac in various tissues from the publication: Chuapoco, M.R., Flytzanis, N.C., Goeden, N. et al. Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain. Nat. Nanotechnol. (2023). https://doi.org/10.1038/s41565-023-01419-x
LBD-case-case-GWAS
By Emma Sherrell onCode used in the analysis from the manuscript Wu et al., Investigation of the genetic aetiology of Lewy body diseases with and without dementia (2023).
Investigation of the genetic aetiology of Lewy body diseases with and without dementia
By Emma Sherrell onPreprint: The authors found that risk alleles rs429358 tagging APOEe4 and rs7668531 near the MMRN1 and SNCA-AS1 genes, increase the odds of developing dementia and that an intronic variant rs17442721 tagging LRRK2 G2019S, on chromosome 12 is protective against dementia. These results should be validated in autopsy confirmed cases in future studies.
UniProtExtractR: an app and R package for easily extracting protein-specific UniProtKB information and fine-tuning organelle resolution
By Emma Sherrell onThe app features interactive frequency tables that globally summarize both the original UniProtKB input query as well as the extracted/changed entry values. Moreover, UniProtExtractR includes a tractable mapping algorithm to define custom organelle-level resolution.
UniProtExtractR
By Emma Sherrell onThe app features interactive frequency tables that globally summarize both the original UniProtKB input query as well as the extracted/changed entry values.
Proteome census upon nutrient stress reveals Golgiphagy membrane receptors
By Emma Sherrell onDuring nutrient stress, macroautophagy is employed to degrade cellular macromolecules, thereby providing biosynthetic building blocks while simultaneously remodeling the proteome. The authors' results, available via an interactive web tool, reveal that autophagic turnover prioritizes membrane-bound organelles (principally Golgi and ER) for proteome remodeling during nutrient stress.
Strep-pull down assay
By Emma Sherrell onStrep pull down assay for FIP200(NTD)-TSF WT or mutants were co-transfected with GST-ATG13(363-517) and/or ULK1(MIT)-MBP.
Protein digestion and mass spectrometry analysis protocol
By Emma Sherrell onThis protocol details a protocol for the trypsin digestion of PI3KC3-C1 and subsequent analysis of digested peptides using LC-MS/MS.
Plasmid construction protocol
By Emma Sherrell onThis protocol details plasmid construction in general terms for the insertion of genes into the pCAG mammalian expression vector.
Preparing mitochondrial samples for immunoblot analysis
By Emma Sherrell onProtocol for preparation of mitochondrial samples for immunoblot analysis.
Molecular dynamics simulations
By Emma Sherrell onThis protocol details molecular dynamics simulations of PI3KC3-C1 on a lipid membrane.
HPLC analysis of nucleotides
By Emma Sherrell onIon-pair reversed phase HPLC analysis of the nucleotide bound to PI3KC3-C1.
Electrospray ionization analysis of eluted nucleotides
By Emma Sherrell onThis protocol describes the denaturation of PI3KC3-C1, and subsequent analysis of eluted nucleotides by electrospray ionization mass spec.
Cryo-EM sample preparation for PI3KC3-C1~RAB1A complex
By Emma Sherrell onThis protocol details cryo-EM sample preparation for PI3KC3-C1~RAB1A complex.
Jensen_etal_2022_molecular_dynamics_simulation_data_2
By Emma Sherrell onFull molecular dynamics simulation data set accompanying Jensen et al, 2022, containing (i) representative coordinates and measurements described therein, (ii) simulation trajectories, and (iii) GROMACS input files.