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Vesicle Scission

Vesicle Scission. The actin cytoskeleton , in tandem with an extended family of membrane-tubulating and severing proteins , may provide the final mechanical action to liberate nascent vesicles from both PM and TGN. actin-binding proteins. lipid-binding properties

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Vesicle Scission

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  1. Vesicle Scission

  2. The actin cytoskeleton, in tandem with an extended family of membrane-tubulating and severing proteins, may provide the final mechanical action to liberate nascent vesicles from both PM and TGN.

  3. actin-binding proteins • lipid-binding properties • deform both the PM and TGN

  4. GTPase dynamin (Dyn) Dyn is well known for its role as a molecular pinchase that assembles as an oligomeric complex in the form of spirals on lipid tubules and at the neck of nascent vesicle buds to help mediate the scission process upon GTP Hydrolysis.

  5. Once : Clathrin mediated endocytosis at the PM. • Now: Dyn 1. mediate vesicle formation 2. function at cellular organelles including the TGN

  6. Conserved Dyn-independent fission mechanisms also exist at the PM and TGN One example: vesicle formation mediated by C-terminal binding protein 3/brefeld in A–ribosylated substrate(CtBP3/BARS). In epithelial cells, CtBP3/BARS mediates the Dyn- independent fissionof basolateral transport carriers from the TGN and fluid-phase endocytosis; However, the exact mechanism of fission is unclear.

  7. Actin-regulatory proteins • Bindproline-rich domain(PRD) • Have membrane-deforming properties. • Contain a Fes/CIP4 homology (FCH) F-BAR for FCH adjacent to a region BAR and EFC for FC • bind to Dyn through a Src-homology 3 (SH3)

  8. As for BAR domain–containing proteins,F- BAR/EFC domain–containing proteins exhibit membrane tubulation activity both in vitro and in vivo. BAR domain–containing proteins are present at the PM and TGN, the F-BAR/EFC domain– containing protein has been implicated in vesicle formation from both the PM and TGN.

  9. Thus… These studies implicate a synergistic action among Dyn, actin, and F-BAR/EFC domain– containing proteins during vesicle formation from both of these sister sites.

  10. Vesicle formation at either the PM or TGN might include a dynamic structural scaffold on which the membrane can be tubulated and vesiculated by a protein complex containing several actin- and lipid-binding proteins. This scission process is not a small task.

  11. Future Directions • The similarities between the clathrin-based vesiculation machinery at both the PM and TGN are strong. • Although differences do exist, it is clear that a central theme of vesicle formation has evolved within the continuum of the two related but distinct sorting stations.

  12. More • How all of these players interact with each other within the confines of a living cell. • How they are regulated during the endocytic and secretory processes • How they malfunction during human disease.

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