A5016937360- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Pancreatic function and diabetes
- Photosynthetic Processes and Mechanisms
- Ion channel regulation and function
- Calcium signaling and nucleotide metabolism
- Cannabis and Cannabinoid Research
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Lipid Membrane Structure and Behavior
- COVID-19 Impact on Reproduction
- Liver Disease Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Transgenic Plants and Applications
- Adenosine and Purinergic Signaling
- RNA Interference and Gene Delivery
- Cholinesterase and Neurodegenerative Diseases
- Autophagy in Disease and Therapy
- Phagocytosis and Immune Regulation
- SARS-CoV-2 and COVID-19 Research
- Tryptophan and brain disorders
National Institute on Drug Abuse
2014-2025
National Institutes of Health
2015-2023
Retention of critical endoplasmic reticulum (ER) luminal proteins needed to carry out diverse functions (e.g., protein synthesis and folding, lipid metabolism) is mediated through a carboxy-terminal ER retention sequence (ERS) its interaction with KDEL receptors. Here, we demonstrate that depleting calcium causes mass departure ERS-containing from cells by overwhelming In addition, provide evidence KDELR2 KDELR3, but not KDELR1, are unfolded response (UPR) genes upregulated as an adaptive...
Endoplasmic reticulum (ER) calcium homeostasis is disrupted in diverse pathologies, including neurodegeneration, cardiovascular diseases, and diabetes. Temporally defining dysregulation during disease progression, however, has been challenging. Here we describe secreted ER calcium-monitoring proteins (SERCaMPs), which allow for longitudinal monitoring of homeostasis. We identified a carboxy-terminal modification that sufficient to confer release protein specifically response depletion. A...
Abstract SARS-CoV-2 E and 3a proteins are important for the assembly, budding, release of viral particles. These two transmembrane have been implicated in forming channels membrane that allow transport ions to favor replication. During an active infection, both generally localize endoplasmic reticulum (ER), ER-Golgi intermediate compartment (ERGIC), Golgi where assembly occurs. The ER critical proper packaging trafficking cellular along secretory pathways which determine a protein’s final...
Endoplasmic reticulum (ER) dysregulation is associated with pathologies including neurodegenerative, muscular, and diabetic conditions. Depletion of ER calcium can lead to the loss resident proteins in a process termed exodosis. To identify compounds that attenuate redistribution under pathological conditions, we performed quantitative high-throughput screen using Gaussia luciferase (GLuc)-secreted modulated protein (SERCaMP) assay, which monitors secretion ER-resident triggered by...
Abstract Dysregulation of synaptic glutamate levels can lead to excitotoxicity such as that observed in stroke, traumatic brain injury, and epilepsy. The role increased intracellular calcium (Ca 2+ ) the development is well established. However, less known regarding impact on endoplasmic reticulum (ER)‐Ca ‐mediated processes proteostasis. To investigate this, we expressed a secreted ER Ca modulated protein (SERCaMP) primary cortical neurons monitor exodosis, phenomenon whereby depletion...
Context: Endoplasmic reticulum (ER) calcium depletion is associated with diverse diseases, including cardiac, hepatic, and neurologic diseases.Objective: The aim of the present study was to identify characterize an endogenous protein that could be used monitor ER comparably a previously described exogenous reporter protein.Materials methods: use selective esterase-fluorescein diester pair allowed for carboxylesterase activity in extracellular fluid measured using fluorescent readout. Cell...
The endoplasmic reticulum (ER) is essential to many cellular processes including protein processing, lipid metabolism and calcium storage. ability longitudinally monitor ER homeostasis in the same organism would offer insight into progressive molecular adaptations physiologic or pathologic states, but has been challenging. We recently described creation of a Gaussia luciferase (GLuc)-based secreted calcium-modulated (SERCaMP GLuc-SERCaMP) homeostasis. Here we describe complementary tool...
The endoplasmic reticulum (ER) contains the highest level of intracellular calcium, with concentrations approximately 5,000-fold greater than cytoplasmic levels. Tight control over ER calcium is imperative for protein folding, modification and trafficking. Perturbations to can result in activation unfolded response, a three-prong stress response mechanism, contribute pathogenesis variety diseases. ability monitor alterations during disease onset progression important principle, yet...
The lumen of the endoplasmic reticulum (ER) has resident proteins that are critical to perform various tasks ER such as protein maturation and lipid metabolism. These typically have a carboxy-terminal retention/retrieval sequence (ERS). canonical ERS promotes retrieval is Lys-Asp-Glu-Leu (KDEL) when an moves from Golgi, KDEL receptors (KDELRs) in Golgi recognize return lumen. Depletion calcium leads mass departure process termed exodosis, which regulated by KDELRs. Here, combining...
Drugs of abuse can cause local and systemic hyperthermia, a known trigger endoplasmic reticulum (ER) stress the unfolded protein response (UPR). Another ER UPR is calcium depletion, which causes exodosis, secretion ER-resident proteins. In rodent models, club drugs such as 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) create hyperthermic conditions in brain toxicity that affected by environmental temperature presence other drugs, caffeine. human studies, MDMA stimulated an acute,...
The endoplasmic reticulum (ER) contains the highest level of intracellular calcium, with concentrations approximately 5,000-fold greater than cytoplasmic levels. Tight control over ER calcium is imperative for protein folding, modification and trafficking. Perturbations to can result in activation unfolded response, a three-prong stress response mechanism, contribute pathogenesis variety diseases. ability monitor alterations during disease onset progression important principle, yet...
Abstract Drugs of abuse can cause local and systemic hyperthermia, a known trigger endoplasmic reticulum (ER) stress the unfolded protein response (UPR). Another ER UPR is calcium depletion which causes exodosis, secretion resident proteins. Club drugs such as 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) create hyperthermic conditions in brain toxicity that affected by environmental temperature presence other drugs, caffeine. Here we examine proteins activation under combined exposure...
The endoplasmic reticulum (ER) is an invaluable component of the secretory pathway; serving as main site for protein synthesis and modification, lipid metabolism, lipoprotein secretion, calcium homeostasis. In response to "stress", ER maintains homeostasis through unfolded (UPR). UPR adaptive employed by alleviate stress caused misfolded proteins. activation mediated three transmembrane proteins; IRE1 (inositolrequiring protein-1), ATF6 (activating transcription factor- 6), PERK (protein...
Maintenance of calcium homeostasis is important for proper endoplasmic reticulum (ER) function. When cellular stress conditions deplete the high concentration in ER, ER-resident proteins are secreted into extracellular space a process called exodosis. Monitoring exodosis provides insight changes ER and proteostasis resulting from associated with dysregulation. To monitor cell-type specific intact animal, we created transgenic mouse line Gaussia luciferase (GLuc)-based, calcium-modulated...
Abstract Dysregulation of synaptic glutamate levels can lead to excitotoxicity such as that observed in stroke, traumatic brain injury, and epilepsy. The role increased intracellular calcium (Ca 2+ ) the development is well established. However, less known regarding impact on endoplasmic reticulum (ER)-Ca -mediated processes proteostasis. To investigate this, we expressed a secreted ER Ca modulated protein (SERCaMP) primary cortical neurons monitor exodosis, phenomenon whereby depletion...
Abstract The lumen of the endoplasmic reticulum (ER) has resident proteins that are critical to perform various tasks ER such as protein maturation and lipid metabolism. These typically have a carboxy-terminal retention sequence (ERS). canonical ERS is Lys-Asp-Glu-Leu (KDEL) when an moves from Golgi, KDEL receptors (KDELRs) in Golgi recognize return lumen. Depletion calcium leads mass departure process termed exodosis, which also regulated by KDELRs. Here, combining computational prediction...