Identification of NIPSNAP1 as a nocistatin-interacting protein involving pain transmission.

Abstract

4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) is a molecule of physiologically unknown function, although it is predominantly expressed in the brain, spinal cord, liver, and kidney. We identified NIPSNAP1 as a protein that interacts with the neuropeptide nocistatin (NST) from synaptosomal membranes of mouse spinal cord using high-performance affinity latex beads. NST, which is produced from the same precursor protein as an opioid-like neuropeptide nociceptin/orphanin FQ (N/OFQ), has opposite effects on pain transmission evoked by N/OFQ. The calculated full-length pre-protein of NIPSNAP1 was 33 kDa, whereas the N-terminal truncated form of NIPSNAP1 (29 kDa) was ubiquitously expressed in the neuronal tissues, especially in synaptic membrane and mitochondria of brain. The 29-kDa NIPSNAP1 was distributed on the cell surface, and NST interacted with the 29-kDa but not the 33-kDa NIPSNAP1. Although intrathecal injection of N/OFQ induced tactile allodynia in both wild-type and NIPSNAP1-deficient mice, the inhibition of N/OFQ-evoked tactile allodynia by NST seen in wild-type mice was completely lacking in the deficient mice. These results suggest that NIPSNAP1 is an interacting molecule of NST and plays a crucial role in pain transmission.

• Authors: Emiko Okuda-Ashitaka, Toshiaki Minami, Shingo Tsubouchi, Hiroshi Kiyonari, Akihiro Iwamatsu, Tetsuo Noda, Hiroshi Handa, Seiji Ito
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 13 Pg. 10403-10413 (Mar 23 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 22311985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Intercellular Signaling Peptides and Proteins
• Membrane Proteins
• NIPSNAP1 protein, human
• Nerve Tissue Proteins
• Nipsnap1 protein, mouse
• Opioid Peptides
• Proteins
• nocistatin

Topics

• Analgesics, Opioid (adverse effects, pharmacology)
• Animals
• Brain (metabolism, pathology)
• COS Cells
• Chlorocebus aethiops
• Humans
• Hyperalgesia (chemically induced, genetics, metabolism, pathology)
• Intercellular Signaling Peptides and Proteins
• Membrane Proteins
• Mice
• Mitochondria (genetics, metabolism)
• Nerve Tissue Proteins (agonists, genetics, metabolism)
• Opioid Peptides (adverse effects, pharmacology)
• Pain (genetics, metabolism)
• Proteins (agonists, genetics, metabolism)
• Spinal Cord (metabolism, pathology)
• Synaptic Membranes (genetics, metabolism)
• Synaptic Transmission (drug effects, genetics)