A5012704232- Polyamine Metabolism and Applications
- Amino Acid Enzymes and Metabolism
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Lipoproteins and Cardiovascular Health
- Lysosomal Storage Disorders Research
- Metabolomics and Mass Spectrometry Studies
- Cannabis and Cannabinoid Research
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Aldose Reductase and Taurine
- Bladder and Urothelial Cancer Treatments
- Lipid metabolism and biosynthesis
- Electrospun Nanofibers in Biomedical Applications
- Advanced Fluorescence Microscopy Techniques
- Health and Conflict Studies
- Skin and Cellular Biology Research
- Urinary and Genital Oncology Studies
- Mast cells and histamine
- Cerebrovascular and genetic disorders
- Cell Image Analysis Techniques
- Spectroscopy and Quantum Chemical Studies
- Urinary Tract Infections Management
University of Helsinki
2013-2024
Minerva Foundation
2013-2023
Helsinki University Hospital
1991
The intracellular transport of cholesterol is subject to tight regulation. structure the lysosomal integral membrane protein type 2 (LIMP-2, also known as SCARB2) reveals a large cavity that traverses molecule and resembles in SR-B1 mediates lipid transfer. detection within LIMP-2 formation cholesterol-like inclusions knockout mice suggested possibility LIMP2 transports lysosomes. We present results molecular modeling, crosslinking studies, microscale thermophoresis cell-based assays support...
Abstract Cholesterol accumulation in late endosomes is a prevailing phenotype of Niemann-Pick type C1 (NPC1) mutant cells. Likewise, annexin A6 (AnxA6) overexpression induces reminiscent NPC1 Here, we demonstrate that this cellular cholesterol imbalance due to AnxA6 promoting Rab7 inactivation via TBC1D15, Rab7-GAP. In cells, depletion and eventual activation was associated with peripheral distribution increased mobility endosomes. This accompanied by an enhanced lipid droplets...
Low-density lipoprotein (LDL)-cholesterol delivery from late endosomes to the plasma membrane regulates focal adhesion dynamics and cell migration, but mechanisms controlling it are poorly characterized. Here, we employed auxin-inducible rapid degradation of oxysterol-binding protein-related protein 2 (ORP2/OSBPL2) show that endogenous ORP2 mediates transfer LDL-derived cholesterol kinase (FAK)-/integrin-positive recycling in human cells. In vitro, enhances association FAK PI(4,5)P2...
ODC (ornithine decarboxylase), the rate-limiting enzyme in polyamine biosynthesis, is regulated by specific inhibitors, AZs (antizymes), which turn are inhibited AZI (AZ inhibitor). We originally identified and cloned cDNA for a novel human ODC-like protein called ODCp (ODC paralogue). Since was devoid of catalytic activity, we proposed that form AZI. has subsequently been suggested to function either as mammalian ADC (arginine decarboxylase) or mice. Here, report (AZIN2). By using yeast...
Recent developments in auxin-inducible degron (AID) technology have increased its popularity for chemogenetic control of proteolysis. However, generation human AID cell lines is challenging, especially embryonic stem cells (hESCs). Here, we develop HiHo-AID2, a streamlined procedure rapid, one-step cancer and hESC with high homozygous degron-tagging efficiency based on an optimized AID2 system homology-directed repair enhancers. We demonstrate application rapid inducible functional...
Background Upon IgE-mediated activation, mast cells (MC) exocytose their cytoplasmic secretory granules and release a variety of bioactive substances that trigger inflammatory responses. Polyamines mediate numerous cellular physiological functions. We report here MCs express antizyme inhibitor 2 (AZIN2), an activator polyamine biosynthesis, previously reported to be exclusively expressed in the brain testis. have investigated intracellular localization AZIN2 both resting activated MCs. In...
Cells store excess lipids as two major compounds, triacylglycerols (TAGs) and cholesteryl esters (CEs), inside lipid droplets (LDs). The degree of ordering is considered to play a role in the mobility enzymatic processing LDs. Here, we provide evidence that polarized third-harmonic generation (THG) microscopy distinguishes between native TAG- CE-enriched LDs cells due different species. We first demonstrate responses from synthetic using THG with linear circular polarizations differ...
Polyamines are small cationic molecules that in adult brain connected to neuronal signaling by regulating inward-rectifier K(+)-channels and different glutamate receptors. Antizyme inhibitors (AZINs) regulate the cellular uptake of polyamines activate ornithine decarboxylase (ODC), rate-limiting enzyme polyamine synthesis. Elevated levels ODC activity detected various disorders including stroke Alzheimer's disease (AD). We originally reported a novel brain- testis-specific AZIN, called...
Ornithine decarboxylase (ODC) antizyme inhibitor 2 (AZIN2), originally called ODCp, is a regulator of polyamine synthesis that we identified and cloned. High expression ODCp mRNA was found in brain testis. We reported AZIN2 involved regulation cellular vesicle transport / or secretion, but the ultimate physiological role(s) still poorly understood. In this study used peptide antibody (K3) to human by immunohistochemistry mapped its various normal tissues. high nervous system, type...
Systematic insight into cellular dysfunction can improve understanding of disease etiology, risk assessment, and patient stratification. We present a multiparametric high-content imaging platform enabling quantification low-density lipoprotein (LDL) uptake lipid storage in cytoplasmic droplets primary leukocyte subpopulations. validate this with samples from 65 individuals variable blood LDL-cholesterol (LDL-c) levels, including familial hypercholesterolemia (FH) non-FH subjects. integrate...
This paper presents the application of polarization-sensitive THG microscopy to examine lipid structures. Significant variations in signals across film under different tightly focused polarizations were observed, suggesting evidence ordered regions work suggests that equipped with polarization-engineered beams can be used as feasible characterization probes for investigating nonlinear optical properties
Auxin-inducible degron (AID) technology is powerful for chemogenetic control of proteolysis. However, generation human cell lines to deplete endogenous proteins with AID remains challenging. Typically, homozygous degron-tagging efficiency low and overexpression an auxin receptor requires additional engineering steps. Here, we establish a one-step genome editing procedure high-efficiency tagging expression. We demonstrate its application in 5 lines, including embryonic stem (ES) cells. The...