A5042977716- Lipid Membrane Structure and Behavior
- Extracellular vesicles in disease
- Cellular transport and secretion
- Hippo pathway signaling and YAP/TAZ
- RNA Interference and Gene Delivery
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Wnt/β-catenin signaling in development and cancer
- Protein Structure and Dynamics
- Blood properties and coagulation
- Ubiquitin and proteasome pathways
- Erythrocyte Function and Pathophysiology
- Connexins and lens biology
- Metabolism, Diabetes, and Cancer
- Protein Degradation and Inhibitors
- ATP Synthase and ATPases Research
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- Axon Guidance and Neuronal Signaling
- Phagocytosis and Immune Regulation
- Receptor Mechanisms and Signaling
- Heat shock proteins research
- Neurobiology and Insect Physiology Research
- PI3K/AKT/mTOR signaling in cancer
- Biomedical Research and Pathophysiology
Centre National de la Recherche Scientifique
2016-2021
KU Leuven
2017-2021
Inserm
2016-2021
Aix-Marseille Université
2016-2021
Centre de Recherche en Cancérologie de Marseille
2016-2021
Institut Paoli-Calmettes
2017-2021
Universidad de Murcia
2012-2014
Significance Viral-like nanovesicles of endosomal origin, or “exosomes,” are newly recognized vehicles signals that cells use to communicate, in various systemic diseases, including cancer. Yet the molecular mechanisms regulate biogenesis and activity exosomes remain obscure. Here, we establish oncogenic protein SRC stimulates secretion loaded with syntenin syndecans, known co-receptors for a plethora signaling adhesion molecules. phosphorylates conserved tyrosine residues syndecans their...
Exosomes, extracellular vesicles (EVs) of endosomal origin, emerge as master regulators cell-to-cell signaling in physiology and disease. Exosomes are highly enriched tetraspanins (TSPNs) syndecans (SDCs), the latter occurring mainly proteolytically cleaved form, membrane-spanning C-terminal fragments proteins. While both protein families membrane scaffolds appreciated for their role exosome formation, composition, activity, we currently ignore whether these work together to control biology....
Abstract Exosomes support cell‐to‐cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition activity a specific manner. Building on our previous understanding how syntenin, its PDZ partner syndecan (SDC), impact we optimized chemical compound targeting the PDZ2 domain syntenin. In vitro , tests MCF‐7 breast carcinoma cells, this is non‐toxic impairs cell proliferation, migration primary sphere...
Abstract PDZ domain-containing proteins work as intracellular scaffolds to control spatio-temporal aspects of cell signalling. This function is supported by the ability their domains bind other such receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure syntenin tandem in complex with carboxy-terminal fragment Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP 2 ). The reveals tripartite interaction formed via second domain...
Abstract Exosomal transfers represent an important mode of intercellular communication. Syntenin is a small scaffold protein that, when binding ALIX, can direct endocytosed syndecans and syndecan cargo to budding endosomal membranes, supporting the formation intraluminal vesicles that compose source major class exosomes. Syntenin, however, also support recycling these same components cell surface. Here, by studying mice cells with syntenin-knock out, we identify syntenin as part dedicated...
Despite the recent advances in cancer therapeutics, highly aggressive forms, such as glioblastoma (GBM), still have very low survival rates. The intracellular scaffold protein syntenin, comprising two postsynaptic density protein-95/discs-large/zona occludens-1 (PDZ) domains, has emerged a novel therapeutic target malignant phenotypes including GBM. Here, we report development of novel, potent, and metabolically stable peptide inhibitor KSL-128114, which binds PDZ1 domain syntenin with...
The C2 domain of PKCα possesses two different binding sites, one for Ca2+ and phosphatidylserine a second that binds PIP2 with very high affinity. enzymatic activity was studied by activating it large unilamellar lipid vesicles, varying the concentration contents dioleylglycerol (DOG), phosphatidylinositol 4,5-bisphosphate (PIP2) phosphadidylserine (POPS) in these model membranes. results showed increased Vmax and, when 5 mol% total membrane, addition 2 DOG did not increase activity. In...
The C2 domain of PKCα (C2α) induces fluorescence self-quenching NBD-PS in the presence Ca2+, which is interpreted as demixing phosphatidylserine from a mixture this phospholipid with phosphatidylcholine. Self-quenching was considerably increased when phosphatidylinositol-4,5-bisphosphate (PIP2) present membrane. When PIP2 labeled phospholipid, form TopFluor-PIP2, induced by also observed, but dependent on phosphatidylserine. An independent indication effect given C2α obtained using 2H-NMR,...
Abstract It is important to understand the biogenesis of exosomes, extracellular vesicles endosomal origin controlling cell-to-cell communication. We previously reported that Phospholipase D2 (PLD2) supports late endosome (LE) budding and syntenin-dependent exosomes. Here, we reveal PLD2 has a broader generic effect on exosome production. Combining gain- loss-of-function experiments, proteomics, microscopy lipid-binding studies with reconstituted liposomes mimicking LE, show that: (i)...