Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons
By savannah onPublication: Learning and consolidating new motor skills require plasticity in the motor cortex and striatum, two key motor regions of the brain. However, how neurons undergo synaptic changes and become recruited during motor learning to form a memory remains unknown. Here the authors identify M1 engram neurons important for memory.
A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice
By savannah onPublication: The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Here, the authors investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. View original preprint.
R1441C and G2019S LRRK2 knock-in mice have distinct striatal molecular, physiological, and behavioral alterations
By savannah onPublication: LRRK2 mutations are closely associated with PD. Convergent evidence suggests that LRRK2 regulates striatal function. Here, by using knock-in mouse lines expressing the two most common LRRK2 pathogenic mutations – G2019S and R1441C – the authors investigated how LRRK2 mutations altered striatal physiology. View original preprint.
Regulatory imbalance between LRRK2 kinase, PPM1H phosphatase, and ARF6 GTPase disrupts the axonal transport of autophagosomes
By savannah onPreprint: Gain-of-function mutations in the LRRK2 gene cause Parkinson's disease (PD), increasing phosphorylation of RAB GTPases through hyperactive kinase activity. The authors found that LRRK2-hyperphosphorylated RABs disrupt the axonal transport of autophagosomes by perturbing the coordinated regulation of cytoplasmic dynein and kinesin motors.
Assay for PhosphoRab activation of LRRK2 Kinase
By savannah onMST kinase phosphorylates Rab proteins are at the same site as LRRK2 and have been used to phosphorylate Rab8A and Rab10 quantitatively. This protocol includes a method to produce phosphoRab8A protein and remove as much contaminating MST3 as possible, to enable use of the phosphoRab to test subsequent activation of LRRK2 kinase.
Assay for Dual Rab GTPase binding to the LRRK2 Armadillo Domain
By savannah onThe LRRK2 Armadillo domain contains multiple Rab GTPase binding sites. To show that the sites can be occupied simultaneously, we use this assay. The idea is to immobilize Rab8A, bind Armadillo domain, and test if phosphoRab10 can bind to Rab8A-immobilized Armadillo domain.
Genome-wide Analysis of Motor Progression in Parkinson Disease
By savannah onPublished: In this article, the authors explored whether there are genetic variants that explain variability in the motor progression found in Parkinson’s in clinical cohorts. They performed a large study genome scan looking at the influence of genetic variation on motor progression and the worsening of motor capabilities among thousands of Parkinson's patients. View original preprint.
Radiolabeled polyamine uptake in cells
By savannah onThis protocol provides a technique to determine the radiolabeled polyamine uptake capacity in cells, via the acquisition of disintegrations per minute (DPM) using a Liquid Scintillation Counter.
Pseudogenes limit the identification of novel common transcripts generated by their parent genes
By savannah onPreprint: Genetic analyses are often complicated by genomic sequences with high sequence similarity. Here, the authors examined the role of pseudogenes on transcriptomic analyses using GB1 and GBAP1 as examples.
Detection of mosaic and population-level structural variants with Sniffles2
By savannah onPublished: The authors developed Sniffles2, a faster and more accurate method to analyze long-ready structural variation calling. This method also solves the problem of family to population-level SV calling to produce fully genotyped VCF files. View original preprint.
Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease
By savannah onPublished: The authors explored the role of resident macrophages in alpha-synuclein-mediated neuroinflammation. They found that border-associated macrophages (BAMs) play a key role in alpha-synuclein induced neuroinflammation where BAMs play a role in immune cell recruitment, infiltration, and antigen presentation. View original preprint.
Distinct adaptations revealed by unbiased proteomic analysis of autophagy cargos in the brain in PINK1 and LRRK2 models of Parkinson’s disease
By savannah onPreprint: Evidence suggests that disruption of autophagy may contribute to PD pathogenesis. Yet, the role it plays is unresolved. The authors used unbiased proteomics to compare basal autophagy to autophagy in two PD-relevant mouse models (PINK1 KO and LRRK2 G2019S). They found different compensatory mechanisms to maintain cellular homeostasis when autophagy is disrupted.
Protein aggregation and calcium dysregulation are the earliest hallmarks of synucleinopathy in human midbrain dopaminergic neurons
By savannah onPreprint: Mutations in the SNCA gene causes PD and aggregates of alpha-synuclein are well known to be present in PD pathology. However, understanding the cellular sequence of events that occurs from mutation to pathology is unresolved. The authors find the temporal sequence of pathophysiological events that occur during neuronal differentiation that likely cause synucleopathies.
Ca2+ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons
By savannah onPublished: The authors explore how cellular energy production and demand are matched. By studying the pacemaking activity of dopaminergic neurons using a combination of electrophysiolocal, optical, and molecular method, they found that spike- activated calcium ion entry triggered calcium ion release from the ER, causing mitochondrial oxidative phosphorylation to occur through two calcium-dependent mechanisms.
Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation
By savannah onPublished: Lipid transport at membrane contact sites is a critical biological process. The authors identify mitoguardin-2, a mitochondrial protein that functions as a lipid transporter at contact sites between the ER and/or lipid droplets. They show that mitoguardin-2 transfers glycerophospholipids between membranes in vitro.
Primary data associated with doi: 10.7554/eLife.67900 (Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain)
By quincy.tichenor onImmunofluorescence microscopy images, raw immunoblotting data, and tabular data used to generate graphs shown in all figures.
Mass spectrometry proteomic data supporting the PPM1H/Rab8A crosslinking study described in doi: 10.15252/embr.202152675
By quincy.tichenor onMass spectrometry proteomic data supporting the PPM1H/Rab8A crosslinking study described in doi: 10.15252/embr.202152675, deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD026367
cDNA clone for bacterial expression of human PPM1H H153D
By quincy.tichenor onPlasmid for bacterial expression of human PPM1H (H153D); contains TEV protease site for removal of 6His tag.
Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration
By quincy.tichenor onReview: Several mutations of genes that encode proteins localized at the endoplasmic reticulum membrane contact sites result in familial neurodegenerative diseases. Here, the authors provide an overview of such diseases, with a specific focus on proteins that directly or indirectly impact lipid transport.
