Abstract
Associations between proteins present on neurotransmitter-containing vesicles and on the presynaptic membrane are thought to underlie docking and fusion of synaptic vesicles with the plasma membrane, which are obligate steps in regulated neurotransmission1–4. SNAP-25 resides on the plasma membrane and interacts with syntaxin (a plasma membrane t-SNARE) and VAMP (a vesicle v-SNARE)1–9 to form a core protein complex thought to be an intermediate in a biochemical pathway that is essential for vesicular transport. We have now characterized a protein, Hrs-2, that interacts with SNAP-25. The binding of Hrs-2 to SNAP-25 is inhibited by calcium in the physiological concentration range that supports synaptic transmission. Furthermore, Hrs-2 binds and hydrolyses nucleoside triphosphates with kinetics that suggest that ATP is the physiological substrate for this enzyme. Hrs-2 is expressed throughout the brain and is present in nerve terminals. Moreover, recombinant Hrs-2 inhibits calcium-triggered 3H-noradrenaline release from permeabilized PC 12 cells. Our results suggest a role for Hrs-2 in regulating secretory processes through calcium- and nucleotide-dependent modulation of vesicle-trafficking protein complexes.
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Bean, A., Seifert, R., Chen, Y. et al. Hrs-2 is an ATPase implicated in calcium-regulated secretion. Nature 385, 826–829 (1997). https://doi.org/10.1038/385826a0
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DOI: https://doi.org/10.1038/385826a0
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