A5069727929- Cellular transport and secretion
- Caveolin-1 and cellular processes
- Lipid Membrane Structure and Behavior
- Erythrocyte Function and Pathophysiology
- Microtubule and mitosis dynamics
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Retinal Development and Disorders
- Protein Structure and Dynamics
- Ion channel regulation and function
- Ion Transport and Channel Regulation
- Multiple Myeloma Research and Treatments
- Angiogenesis and VEGF in Cancer
- Calcium signaling and nucleotide metabolism
- Genetic and Kidney Cyst Diseases
- Research on Leishmaniasis Studies
- Biomedical Research and Pathophysiology
- Cardiovascular Health and Risk Factors
- Signaling Pathways in Disease
- Genomics, phytochemicals, and oxidative stress
- Hedgehog Signaling Pathway Studies
- Tea Polyphenols and Effects
- Drug Transport and Resistance Mechanisms
- Glutathione Transferases and Polymorphisms
Vanderbilt University
2014-2023
University of Virginia
2020-2023
University of Iowa
2009-2013
Abstract The intracellular ciliogenesis pathway requires membrane trafficking, fusion, and reorganization. Here, we demonstrate in human cells zebrafish that the F-BAR domain containing proteins PACSIN1 -2 play an essential role ciliogenesis, similar to their binding partner reorganizer EHD1. In mature cilia, PACSINs EHDs are dynamically localized ciliary pocket (CPM) transported away from this structure on tubules along with exit cilium. function early at vesicle (CV) stage promote mother...
How the plasma membrane is bent to accommodate clathrin-independent endocytosis remains uncertain. Recent studies suggest Shiga and cholera toxin induce curvature required for their uptake into carriers by binding cross-linking multiple copies of glycosphingolipid receptors on membrane. But it unclear if toxin-induced sphingolipid crosslinking provides sufficient mechanical force deforming membrane, or host cell factors also contribute this process. To test this, we imaged B-subunit...
The α5β1 integrin heterodimer regulates many processes that contribute to embryonic development and angiogenesis, in both physiological pathological contexts. As one of the major adhesion complexes on endothelial cells, it plays a vital role migration along extracellular matrix. We recently showed angiogenesis is modulated by syntaxin 6, Golgi- endosome-localized t-SNARE, does so regulating post-Golgi trafficking VEGFR2. Here we show 6 also required for integrin-mediated cells to, along,...
Vascular endothelial growth factor receptor-2 (VEGFR2) is a receptor tyrosine kinase that expressed in cells and regulates angiogenic signal transduction under both physiological pathological conditions. VEGFR2 turnover at the plasma membrane (PM) regulated by its transport through endocytic secretory pathways. Short-range cargo trafficking along actin filaments commonly motor proteins of myosin superfamily. In current study, performed primary human cells, we demonstrate unconventional 1c...
IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces therapy resistance, but the resistance mechanisms remain unclear. The present study determines role of IL-6 in re-establishing intracellular redox homoeostasis context therapy. treatment increased cell to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative alone, cells treated with plus demonstrated reduced annexin/propidium iodide staining, caspase 3...
Caveolin-1 (CAV1) is an essential component of caveolae and implicated in numerous physiological processes. Recent studies have identified heterozygous mutations the CAV1 gene patients with pulmonary arterial hypertension (PAH), but mechanisms by which these impact assembly contribute to disease remain unclear. To address this question, we examined consequences a familial PAH-associated frameshift mutation CAV1, P158PfsX22, on function. We show that C-terminus P158 protein contains...
The soluble form of vascular endothelial growth factor receptor 1 (sVEGFR-1/sFlt1) is generated by alternative splicing the FLT1 gene. Secretion sFlt1 from cells plays an important role in blood vessel sprouting and morphogenesis. However, excess secretion associated with diseases such as preeclampsia chronic kidney disease. To date, secretory transport process involved poorly understood. In present study, we investigated itinerary trafficking along pathway. understand timecourse secretion,...
Processing of the amyloid precursor protein (APP) via amyloidogenic pathway is associated with etiology Alzheimer's disease. The cleavage APP by β-secretase to generate transmembrane 99-residue C-terminal fragment (C99) and subsequent processing C99 γ-secretase yield amyloid-β (Aβ) peptides are essential steps in this pathway. Biochemical evidence suggests that occurs cholesterol- sphingolipid-enriched liquid-ordered phase membrane rafts. However, direct preferentially associates these rafts...
Caveolin-1 (Cav1) is the primary scaffolding protein of caveolae, flask-shaped invaginations plasma membrane thought to function in endocytosis, mechanotransduction, signaling and lipid homeostasis. A significant amount our current knowledge about caveolins caveolae derived from studies transiently overexpressed, C-terminally tagged caveolin proteins. However, how different tags affect behavior ectopically expressed Cav1 still largely unknown. To address this question, we performed a...
Plasma membrane organization profoundly impacts cellular functionality. A well-known mechanism underlying this is through nanoscopic clustering of distinct lipids and proteins in rafts. Despite their physiological importance, rafts remain a difficult-to-study aspect organization, part because the paucity chemical tools to experimentally modulate properties. Methods selectively target for therapeutic purposes are also currently lacking. To tackle these problems, we developed high-throughput...
Caveolin-1 (CAV1) is a membrane-sculpting protein that oligomerizes to generate flask-shaped invaginations of the plasma membrane known as caveolae. Mutations in CAV1 have been linked multiple diseases humans. Such mutations often interfere with oligomerization and intracellular trafficking processes required for successful caveolae assembly, but molecular mechanisms underlying these defects not structurally explained. Here, we investigate how disease-associated mutation one most highly...
Caveolin-1 (Cav1) drives the formation of flask-shaped membrane invaginations known as caveolae that participate in signaling, clathrin-independent endocytosis and mechanotransduction. Overexpression or mutations Cav1 can lead to its mistrafficking, including accumulation a perinuclear compartment previously identified Golgi complex. Here, we show case overexpressed Cav1-GFP, this consists cytoplasmic inclusion bodies generated response aggregates misfolded proteins, aggresomes. Aggresomes...
The formation and maintenance of cell-cell junctions, both under physiological pathological conditions, requires the targeting trafficking junctional proteins. Proteins syntaxin (Stx)-family localize to a variety subcellular membranes contribute intracellular transport cargo by regulating vesicle fusion events at these sites. Unlike plasma membrane localized Stxs, roles endosome- Golgi-localized stx proteins in epithelial morphogenesis are less understood. Here we show that Stx16– an...
The soluble form of vascular endothelial growth factor receptor 1 (sVEGFR-1/sFlt1) is generated by alternative splicing the FLT1 gene.Secretion sFlt1 from cells plays an important role in blood vessel sprouting and morphogenesis.However, excess secretion associated with diseases such as preeclampsia chronic kidney disease.To date, secretory transport process involved poorly understood.In present study, we investigated itinerary trafficking along pathway.To understand timecourse secretion,...
ABSTRACT Caveolin-1 (CAV1) is a membrane sculpting protein that oligomerizes to generate flask-shaped invaginations of the plasma known as caveolae. Mutations in CAV1 have been linked multiple diseases humans. Such mutations often interfere with oligomerization and intracellular trafficking processes required for successful caveolae assembly, but molecular mechanisms underlying these defects not structurally explained. Here, we investigate how breast cancer-associated mutation one most...