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Biomedical subjects

Alexander Stein

Publications and source records attributed to Alexander Stein.

5 recordsLinked to original sources
PubMed2006

N- to C-terminal SNARE complex assembly promotes rapid membrane fusion.

Assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) syntaxin 1, SNAP-25, and synaptobrevin 2 is thought to be the driving force for the exocytosis of synaptic vesicles. However, whereas exocytosis is triggered at a millisecond time scale, the SNARE-mediated fusion of liposomes requires hours for completion, which challenges the idea of a key role for SNAREs in the final steps of exocytosis. We found that liposome fusion was dramatically accelerated when a stabilized syntaxin/SNAP-25 acceptor complex was used. Thus, SNAREs do have the capacity to execute fusion at a speed required for neuronal secretion, demonstrating that the maintenance of acceptor complexes is a critical step in biological fusion reactions.

Amino Acid Sequence↗
PubMed2005

Distinct kinetic changes in neurotransmitter release after SNARE protein cleavage.

Neurotransmitter release is triggered by calcium ions and depends critically on the correct function of three types of SNARE [soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor] proteins. With use of the large calyx of Held presynaptic terminal from rats, we found that cleavage of different SNARE proteins by clostridial neurotoxins caused distinct kinetic changes in neurotransmitter release. When elevating calcium ion concentration directly at the presynaptic terminal with the use of caged calcium, cleavage of SNAP-25 by botulinum toxin A (BoNT/A) produced a strong reduction in the calcium sensitivity for release, whereas cleavage of syntaxin using BoNT/C1 and synaptobrevin using tetanus toxin (TeNT) produced an all-or-nothing block without changing the kinetics of remaining vesicles. When stimulating release by calcium influx through channels, a difference between BoNT/C1 and TeNT emerged, which suggests that cleavage of synaptobrevin modifies the coupling between channels and release-competent vesicles.

Action Potentials↗
PubMed2004

Determinants of liposome fusion mediated by synaptic SNARE proteins.

Synaptic exocytosis requires the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin 1, SNAP-25, and synaptobrevin (VAMP). Assembly of the SNAREs into a stable core complex is supposed to catalyze membrane fusion, and proteoliposomes reconstituted with synaptic SNARE proteins spontaneously fuse with each other. We now show that liposome fusion mediated by synaptic SNAREs is inhibited by botulinum neurotoxin E (BoNT/E) but can be rescued by supplementing the C-terminal portion of SNAP-25. Furthermore, fusion is prevented by a SNAP-25-specific antibody known to block exocytosis in chromaffin cells, and it is competed for by soluble fragments of the R-SNAREs synaptobrevin 2, endobrevin/VAMP-8, and tomosyn. No accumulation of clustered vesicles is observed during the reaction. Rapid artificial clustering of SNARE-containing proteoliposomes enhances the fusion rate at low but not at saturating liposome concentrations. We conclude that the rate of liposome fusion is dominated by the intrinsic properties of the SNAREs rather than by the preceding docking step.

Animals↗
PubMed2004

Music, mourning, and consolation.

The attacks of September 11, 2001, prompt a consideration of the role of music in mourning and trauma. The intrapsychic functions of music in the mourning process are explored, as is music as a unique response to trauma and as a special aesthetic expression of a range of affects connected with grief. Also explored is the allied notion of consolation, a topic underdeveloped in the analytic literature.

Adaptation, Psychological↗