Hrs-2 is an ATPase implicated in calcium-regulated secretion

Nature. 1997 Feb 27;385(6619):826-9. doi: 10.1038/385826a0.


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 neurotransmission. SNAP-25 resides on the plasma membrane and interacts with syntaxin (a plasma membrane t-SNARE) and VAMP (a vesicle v-SNARE) 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 PC12 cells. Our results suggest a role for Hrs-2 in regulating secretory processes through calcium- and nucleotide-dependent modulation of vesicle-trafficking protein complexes.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Brain / metabolism
  • Calcium / metabolism*
  • Endosomal Sorting Complexes Required for Transport
  • Exocytosis
  • Humans
  • Membrane Proteins*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Norepinephrine / metabolism*
  • Nucleotidases / metabolism
  • PC12 Cells
  • Phosphoproteins*
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Synapses / metabolism
  • Synaptosomal-Associated Protein 25
  • Zinc Fingers


  • Endosomal Sorting Complexes Required for Transport
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • SNAP25 protein, human
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Nucleotidases
  • Adenosine Triphosphatases
  • Hgs protein, rat
  • Calcium
  • Norepinephrine

Associated data

  • GENBANK/U87863