A5055104723- Cellular transport and secretion
- Erythrocyte Function and Pathophysiology
- Ion Transport and Channel Regulation
- Barrier Structure and Function Studies
- Cell Adhesion Molecules Research
- Caveolin-1 and cellular processes
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Electrolyte and hormonal disorders
- Parkinson's Disease Mechanisms and Treatments
- Lipid Membrane Structure and Behavior
- Ubiquitin and proteasome pathways
- Advanced Neuroimaging Techniques and Applications
- Alzheimer's disease research and treatments
- CRISPR and Genetic Engineering
- Retinal Development and Disorders
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- Connexins and lens biology
- Microtubule and mitosis dynamics
- Drug Transport and Resistance Mechanisms
- Photoreceptor and optogenetics research
- Nanoparticle-Based Drug Delivery
- Magnesium in Health and Disease
- Neonatal Respiratory Health Research
Aarhus University
2018-2024
Umeå University
2011-2018
University of Copenhagen
2010-2011
The conditional use of actin during clathrin-mediated endocytosis in mammalian cells suggests that the cell controls whether and how is used. Using a combination biochemical reconstitution culture, we elucidate mechanism by which coincidence PI(4,5)P2 PI(3)P curved vesicle triggers polymerization. At clathrin-coated pits, produced INPP4A hydrolysis PI(3,4)P2, this necessary for actin-driven endocytosis. Both Cdc42⋅guanosine triphosphate SNX9 activate N-WASP–WIP- Arp2/3-mediated nucleation....
Caveolae are invaginations of the cell surface thought to regulate membrane tension, signalling, adhesion and lipid homeostasis due their dynamic behaviour ranging from stable association rounds fission fusion with plasma membrane. The caveolae coat is generated by oligomerisation protein caveolin family cavin proteins. Here, we show that cavin3 targeted cavin1 where it interacts scaffolding domain caveolin1 promote dynamics. We found N-terminal region binds a trimer N-terminus in...
Cellular blebbing, caused by local alterations in cell-surface tension, has been shown to increase the invasiveness of cancer cells. However, regulatory mechanisms balancing dynamics and bleb formation remain elusive. Here, we show that an acute reduction cell volume activates clathrin-independent endocytosis. Hence, a decrease surface tension is buffered internalization plasma membrane (PM) lipid bilayer. Membrane invagination endocytosis are driven tension-mediated recruitment sculpting...
Parkinson's disease is mainly caused by aggregation of α-synuclein (α-syn) in the brain. Exchange α-syn between brain and peripheral tissues could have important pathophysiological therapeutic implications, but trafficking mechanism across blood brain-barrier (BBB) remains unclear. In this study, we therefore investigated uptake transport mechanisms monomers oligomers an vitro BBB model system. Both were internalized primary endothelial cells, with increased restriction oligomeric over...
Abstract The detailed mechanisms by which the transferrin receptor (TfR) and associated ligands traffic across brain capillary endothelial cells (BECs) of CNS-protective blood–brain barrier constitute an important knowledge gap within maintenance regulation iron homeostasis. This also presents a major obstacle in research aiming to develop strategies for efficient receptor-mediated drug delivery brain. While TfR-mediated trafficking from blood have been widely studied, investigation has...
Changes in cell morphology require coordination of plasma membrane turnover and cytoskeleton dynamics, processes that are regulated by Rho GTPases. Here, we describe how a direct interaction between the GTPase Cdc42 activating protein (GAP) GRAF1, facilitate rapid surface at leading edge. Both GRAF1 were required for fluid phase uptake generation transient GRAF1-coated endocytic carriers, distinct from clathrin coated vesicles. was found to transiently assemble discrete Cdc42-enriched...
Adaptation of cell shape and polarization through the formation retraction cellular protrusions requires balancing endocytosis exocytosis combined with fine-tuning local activity small GTPases like Rab8. Here, we show that endocytic turnover plasma membrane at is directly coupled to surface removal inactivation Removal induced by reduced tension mediated GTPase regulator associated focal adhesion kinase-1 (GRAF1, also known as ARHGAP26), a clathrin-independent endocytosis. GRAF1-depleted...
The epidermal growth factor receptor (EGFR) is an important regulator of normal and differentiation, it involved in the pathogenesis many cancers. Endocytic downregulation central terminating EGFR signaling after ligand stimulation. It has been shown that p38 MAPK activation also can induce endocytosis. This endocytosis lacks characteristics ligand-induced We compared two types with regard to requirements for proteins internalization machinery. Both require clathrin, but while (EGF)-induced...
Aquaporin-5 (AQP5) is a plasma membrane water channel mainly expressed in secretory glands. Increased expression of AQP5 observed multiple cancers, including breast cancer, where high correlates with the degree metastasis and poor prognosis. Moreover, studies cancer cells have suggested that activates Ras signaling, drives morphological changes, particular increased invasiveness. To design intervention strategies, it utmost importance to characterize dissect cell biological changes induced...
Endocytic mechanisms have been suggested to be important for plasma membrane repair in response pore-forming toxins such as Listeriolysin O (LLO), which form pores that disrupts cellular homeostasis. Yet, little is known about the specific role of distinct endocytic machineries this process. Here, we addressed importance key pathways, and developed reporter systems real-time imaging LLO pore formation. We found loss clathrin-independent pathways negatively influenced efficiency repair....
Abstract Background Blood-brain barrier (BBB) models based on primary murine, bovine, and porcine brain capillary endothelial cell cultures have long been regarded as robust with appropriate properties to examine the functional transport of small molecules. However, species differences sometimes complicate translating results from these human settings. During last decade, endothelial-like cells (BCECs) generated stem sources model BBB in vitro. The aim present study was establish...
Here, we report an experimental setup to benchmark different receptors for targeted therapeutic antibody delivery at the blood-brain barrier. We used brain capillary endothelial-like cells derived from induced pluripotent stem (hiPSC-BECs) as a model system and compared them colon epithelial Caco-2 cells. This approach helped identify favourable transport into cell layer itself or directing transcytosis across layer. The sorting transferrin receptor sortilin were shown be efficient cargo...
Arginine vasopressin (AVP) mediates water reabsorption in the kidney collecting ducts through regulation of aquaporin-2 (AQP2). Also, estrogen has been known to regulate AQP2. Consistently, we previously demonstrated that tamoxifen (TAM), a selective receptor modulator, attenuates downregulation AQP2 lithium-induced nephrogenic diabetes insipidus (NDI). In this study, investigated AVP-independent by TAM and therapeutic effect on dysregulation impaired urinary concentration unilateral...
Regulated vesicle exocytosis is a key response to extracellular stimuli in diverse physiological processes, including hormone regulated short-term urine concentration. In the renal collecting duct, water channel aquaporin-2 (AQP2) localizes apical plasma membrane as well small, subapical vesicles. stimulation with antidiuretic hormone, arginine vasopressin, aquaporin-2-containing vesicles fuse membrane, which increases duct reabsorption and thus, The nanoscale size of these has limited...
Aquaporin-2 (AQP2) fine tunes urine concentration in response to the antidiuretic hormone vasopressin. In addition, AQP2 has been suggested promote cell migration and epithelial morphogenesis. A system allowing temporal quantitative control of expression levels phospho-mimicking mutants missing, as a fluorescently tagged for time-lapse imaging. present study, we generated validated Flp-In T-REx Madin-Darby canine kidney mutants. We verified that can be temporally quantitatively controlled...
Receptor mediated transport of therapeutic antibodies through the blood-brain barrier (BBB) give promise for drug delivery to alleviate brain diseases. We developed a low-cost method obtain nanoscale localization data putative cargo receptors. combine existing ex vivo isolation methods with expansion microscopy (ExM) analyze receptor localizations in microcapillaries. Using this approach, we show how endothelial cells microcapillaries relation abluminal marker collagen IV. By choosing...
Abstract The epidermal growth factor receptor (EGFR) is an important regulator of normal and differentiation, it involved in the pathogenesis many cancers. Endocytic downregulation central terminating EGFR signalling after ligand stimulation, this fairly well known. Recently, has been shown that also p38 MAPK activation can stimulate endocytosis. This endocytosis differs from ligand-induced internalization by lacking hallmarks normally necessary for EGFR. We compared two kinds with regard to...
Abstract Parkinson’s disease is mainly caused by aggregation of α-synuclein (α-syn) in the brain. Exchange α-syn between brain and peripheral tissues could have important pathophysiological therapeutic implications, but trafficking mechanism across blood barrier (BBB) remains unclear. In this study, we therefore investigated uptake transport mechanisms monomers oligomers an vitro BBB model system. Both were internalized primary endothelial cells, with increased restriction oligomeric over...