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Dirk Fasshauer "Structural and Evolutionary Insights into the Vesicle Fusion Machinery"

Abstract :

Structural and evolutionary insights into the vesicle fusion machinery.

Transport of cargo between organelles in eukaryotic cells is mediated by vesicles that bud from a donor compartment and specifically fuse with an acceptor membrane. Currently, it is becoming clear that the underlying molecular machineries involved in the principal aspects of vesicular trafficking are highly conserved. The central machinery involved in the fusion process is composed of members of the SNARE protein family. Distinctive, heterologous sets of SNARE proteins anchored in the vesicle and target membrane are thought to assemble in a zipper-like fashion into a four-helix bundle, providing the energy to mediate fusion of the two bilayers. Although SNAREs are sufficient to drive membrane fusion when inserted into liposome membranes, this minimal machinery is organized and controlled by additional factors in vivo. Members of the cytosolic Sec1/Munc18 (SM) family of proteins have been established as essential factors in different intracellular transport steps, during which they functionally interact with the SNARE machinery. However, the molecular basis for this interplay is not entirely understood. Despite their high sequence conservation, structurally disparate binding modes for SM proteins with their cognate syntaxin SNARE proteins have been observed. In neuronal secretion, the SM protein Munc18a binds to a closed conformation of syntaxin 1a. Our data suggest that this tight interaction enables Munc18a to control the accessibility of syntaxin 1a to its partner SNAREs SNAP-25 and synaptobrevin, a role that might be common to all SM proteins.

Selected publications

SNAREing the basis of multicellularity: Consequences of protein family expansion during evolution
Tobias H. Kloepper; C. Nickias Kienle; Dirk Fasshauer
Molecular Biology and Evolution 2008;
Nagy G, Milosevic I, Mohrman R, Wiederhold K, Walter AM, Sørensen JB.
The SNAP-25 Linker as an Adaptation Towards Fast Exocytosis. Mol Biol Cell. 2008 Jun 25.
Burkhardt P, Hattendorf DA, Weis WI, Fasshauer D.
Munc18a controls SNARE assembly through its interaction with the syntaxin N-peptide.
EMBO J. 2008 Apr 9;27(7):923-33.
Barszczewski M, Chua JJ, Stein A, Winter U, Heintzmann R, Zilly FE, Fasshauer D, Lang T, Jahn R.
A Novel Site of Action for {alpha}-SNAP in the SNARE Conformational Cycle Controlling Membrane Fusion.
Mol Biol Cell. 2008 Mar;19(3):776-84.

Christophe Mulle