<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Molecular Dominoes: The interplay between FGF2 oligomerization and PI(4,5)P2 clustering in membrane pore formation"^^ . "Within the fibroblast growth factor family, fibroblast growth factor 2 (FGF2), a potent mitogen,\r\nfollows an unconventional secretory pathway (UPS), as FGF2 does not contain a signal peptide\r\nthat directs the protein for classical ER/Golgi export. It is able to translocate directly across\r\nthe plasma membrane (type I UPS). This mechanism involves sequential interactions with\r\ncellular components at the plasma membrane. The cytosolic ɑ1 domain of the Na,K-ATPase\r\nrecruits FGF2 to the membrane. FGF2 then interacts with Tec kinase, phosphorylaHng FGF2.\r\nFGF2 binds to the phosphoinositide PI(4,5)P2 lipids in the inner leaflet of the plasma\r\nmembrane, leading to oligomerization and membrane insertion. The translocation is then\r\ncompleted by membrane-proximal heparan sulfate chains of heparan sulfate proteoglycans,\r\nwhich outcompete PI(4,5)P2 in the mutually exclusive binding site, making the translocation\r\nunidirecHonal and irreversible. Bound to the cell surface, FGF2 can exert its function in\r\nautocrine and paracrine signaling. Direct visualization of single secretion events from living\r\ncells by total internal reflection microscopy (TIRF) revealed an average time interval of 200 ms\r\nfrom FGF2 recruitment at the inner plasma membrane leaflet to full translocation to cell\r\nsurfaces. Reconstitution of FGF2 translocation in giant unilamellar vesicles identified FGF2, a\r\nPI(4,5)P2-containing membrane, and luminal long-chain heparin as the minimal component\r\nsystem for translocation. The average FGF2 oligomer size for pore formation was determined\r\nby fluorescence brightness analysis to be four to eight monomers, both in vitro and in cells.\r\nUsing Molecular Dynamics simulations, I demonstrated that the C95-C95 disulfide-bridged\r\nFGF2 dimer self-assembles into oligomers on flat, PI(4,5)P2-containing membranes to induce\r\na substantial, spatially-confined membrane remodeling event. The FGF2 oligomer gathered 4\r\nto 5 of the negatively charged PI(4,5)P2 molecules per FGF2 monomer, thereby creating a\r\nstrong, local electrical charge gradient across the membrane. In addition, PI(4,5)P2\r\naccumulation caused negaHve curvature deformaHons underneath the FGF2 oligomer.\r\nCombined with a very high concentration of non-bilayer lipids such as PI(4,5)P2 and\r\nphosphatidylethanolamine, these effects generate spatially confined stress on the membrane,\r\nwhich I propose to be the primary driving force for membrane pore formation, the process\r\nthat mediates unconventional secretion of FGF2 into the extracellular space."^^ . "2025" . . . . . . . "Daniel"^^ . "Beyer"^^ . "Daniel Beyer"^^ . . . . . . "Molecular Dominoes: The interplay between FGF2 oligomerization and PI(4,5)P2 clustering in membrane pore formation (PDF)"^^ . . . "PhDThesis-DanielBeyer.pdf"^^ . . . "Molecular Dominoes: The interplay between FGF2 oligomerization and PI(4,5)P2 clustering in membrane pore formation (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Molecular Dominoes: The interplay between FGF2 oligomerization and PI(4,5)P2 clustering in membrane pore formation (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Molecular Dominoes: The interplay between FGF2 oligomerization and PI(4,5)P2 clustering in membrane pore formation (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Molecular Dominoes: The interplay between FGF2 oligomerization and PI(4,5)P2 clustering in membrane pore formation (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Molecular Dominoes: The interplay between FGF2 oligomerization and PI(4,5)P2 clustering in membrane pore formation (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #36870 \n\nMolecular Dominoes: The interplay between FGF2 oligomerization and PI(4,5)P2 clustering in membrane pore formation\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .