T Schraw | PubMed Health

PubMed2001

N-ethylmaleimide sensitive factor (NSF) structure and function.

Our understanding of the molecular mechanisms of membrane trafficking advanced at a rapid rate during the 1990s. As one of the initial protein components of the trafficking machinery to be identified, N-ethylmaleimide sensitive factor (NSF) has served as a reference point in many of these recent studies. This hexameric ATPase is essential for most of the membrane-trafficking events in a cell. Initially, due to its ATPase activity, NSF was thought to be the motor that drove membrane fusion. Subsequent studies have shown that NSF actually plays the role of a chaperone by activating SNAP receptor proteins (SNAREs) so that they can participate in membrane fusion. In this review we will examine the initial characterization of NSF, its role in membrane fusion events, and what new structural information can tell us about NSF's mechanism of action.

Adenosine Triphosphatases↗

PubMed2000

Molecular mechanisms of platelet exocytosis: role of SNAP-23 and syntaxin 2 and 4 in lysosome release.

On stimulation by strong agonists, platelets release the contents of 3 storage compartments in 2 apparent waves of exocytosis. The first wave is the release of alpha- and dense core granule contents and the second is the release of lysosomal contents. Using a streptolysin O-permeabilized platelet exocytosis assay, we show that hexosaminidase release is stimulated by either Ca(++) or by GTP-gamma-S. This release step retains the same temporal separation from serotonin release as seen in intact platelets. This assay system was also used to dissect the molecular mechanisms of lysosome exocytosis. Lysosome release requires adenosine triphosphate and the general membrane fusion protein, N-ethylmaleimide sensitive factor. Uniquely, 2 syntaxin t-SNAREs, syntaxin 2 and 4, which localize to granules and open canalicular membranes, together with the general target membrane SNAP receptor (t-SNARE) protein SNAP-23 appear to make up the heterodimeric t-SNAREs required for lysosome exocytosis. These studies further show that regardless of stimuli (Ca(++) or GTP-gamma-S) serotonin and hexosaminidase release requires the same membrane fusion machinery. (Blood. 2000;96:1782-1788)

Antigens, Surface↗