New Insights Into The Transport Machinery Of The Cell: A Single Protein,,Substitutes The Regulatory Machinery Specifying Endosome Fusion In Vitro

Endosomes are a good system to study how cells organise their internal transport logistics. Cells constantly internalise material from the external of the cell and distribute it to the other cellular compartments via specific organelles called endosomes. To bridge the distance between the cell surface and the endosomes, small membrane engulfed vesicles bud from the cell surface like soap bubbles and surround the cargo. Inside the cells there are thousands of such shuttle vesicles that have an important task: to specifically find their target organelle, dock with it and deliver their cargo by fusing with the target membrane. These organelles are surrounded by cytosol, the aqueous solution making up the inside of the cell and through which the vesicles navigate. The complexity comes from the fact that cytosol contains thousands of molecules and for a long time only a few have been recognised to regulate the specificity of the docking and fusing process. Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden/Germany, the European Molecular Biology Laboratory (EMBL) and collaborators from the University of Liverpool now successfully used purification and in vitro experiments to analyse the cytosolic proteins essential for this complex biological mechanism. They reported the new findings in this week's issue of "Nature" (Nature, Vol. 397, 18 February 1999).

In a first step it was necessary to separate proteins, which are involved in the regulation of endosome fusion from those, which are not. Starting point of this strategy was a family of proteins called Rabs, which are established key players in the activation of vesicle docking and fusion. Rabs act as molecular switches alternating between two stages: when active, they allow vesicle membranes to dock and fuse their targets, in their inactive state, fusion doesn't occur. "Rab5" is known to be a key player responsible for fusion of vesicles coming from the cell surface with

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