Output Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
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Membrane remodeling properties of the Parkinson’s disease protein LRRK2
Preprint: The authors examine how purified LRRK2 directly binds acidic lipid bilayers in a cell-free system and can deform them into narrow tubules in a guanylnucleotide-dependent but ATP-independent way.
SHIP164 is a chorein motif lipid transfer protein that controls endosome-Golgi membrane traffic
Cellular membranes differ in protein and lipid composition as well as in the protein-lipid ratio. Thus, progression of membranous organelles along traffic routes requires mechanisms to control bilayer lipid chemistry and their abundance relative to…
RBG Motif Bridge-Like Lipid Transport Proteins: Structure, Functions, and Open Questions
The life of eukaryotic cells requires the transport of lipids between membranes, which are separated by the aqueous environment of the cytosol. Vesicle-mediated traffic along the secretory and endocytic pathways and lipid transfer proteins (LTPs)…
A possible role for VPS13-family proteins in bulk lipid transfer, membrane expansion and organelle biogenesis
At organelle–organelle contact sites, proteins have long been known to facilitate the rapid movement of lipids. Classically, this lipid transport involves the extraction of single lipids into a hydrophobic pocket on a lipid transport protein.…
Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by defective dopaminergic (DAergic) input to the striatum. Mutations in two genes encoding synaptically enriched clathrin-uncoating factors, synaptojanin 1 (SJ1) and…
Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation
Lipid transport proteins at membrane contacts, where organelles are closely apposed, are critical in redistributing lipids from the endoplasmic reticulum (ER), where they are made, to other cellular membranes. Such protein-mediated transfer is…
Erythroid Differentiation Dependent Interaction of VPS13A with XK at the Plasma Membrane of K562 Cells
Mutations in VPS13A and XK lead to Chorea Acanthocytosis and McLeod syndrome, causing neurodegeneration and abnormal red blood cells. VPS13A binds XK at the ER and plasma membrane contacts in differentiated erythroblasts.
Structural and biochemical insights into lipid transport by VPS13 proteins
VPS13 proteins are proposed to function at contact sites between organelles as bridges for lipids to move directionally and in bulk between organellar membranes. VPS13s are anchored between membranes via interactions with receptors, including both…
Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9
Autophagy is a cellular degradation pathway essential for neuronal health and function. Autophagosome biogenesis occurs at synapses, is locally regulated, and increases in response to neuronal activity. The mechanisms that couple autophagosome…
In situ architecture of the lipid transport protein VPS13C at ER–lysosome membrane contacts
Loss-of-function mutations in VPS13C are responsible for rare cases of familial early onset Parkinson’s disease. Using cryo-ET, the authors provide in-situ evidence for a bridge-model of VPS13 in lipid transport.
LRRK2 suppresses lysosome degradative activity in macrophages and microglia through MiT-TFE transcription factor inhibition
Cells maintain optimal levels of lysosome degradative activity to protect against pathogens, clear waste, and generate nutrients. Here, we show that LRRK2, a protein that is tightly linked to Parkinson’s disease, negatively regulates lysosome…
ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling
Mutations in VPS13C cause early onset, autosomal recessive Parkinson’s Disease (PD). We have established that VPS13C encodes a lipid transfer protein localized to contact sites between the endoplasmic reticulum (ER) and late endosomes/lysosomes.…
Phosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits
Study shows increasing PGK1 gene expression enhances neuronal ATP production, protecting against synaptic dysfunction in Parkinson's disease. Boosting bioenergetics with PGK1 may be a promising therapeutic approach for PD.
iATPSnFR2: A high-dynamic-range fluorescent sensor for monitoring intracellular ATP
Improved iATPSnFR2 sensor offers real-time ATP level monitoring in cells. Enhanced dynamic range, high specificity, and subcellular targeting capabilities enable detailed metabolic analysis in different cellular regions.
A STING-CASM-GABARAP Pathway Activates LRRK2 at Lysosomes
Mutations that increase LRRK2 kinase activity have been linked to Parkinson’s disease and Crohn’s disease. LRRK2 is also activated by lysosome damage evoked by chemical and pathogenic stimuli. However, the endogenous cellular mechanisms that…
