Identification of NIPSNAP1 as a nocistatin-interacting protein involving pain transmission.
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.
Department of Medical Chemistry, Kansai Medical University, Moriguchi 570-8506, Japan,; Department of Biomedical Engineering, Osaka Institute of Technology, Osaka 535-8585, Japan,. Electronic address: ashitaka@bme.oit.ac.jp.
Emiko
E
Okuda-Ashitaka
Department of Anesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan.
Toshiaki
T
Minami
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Shingo
S
Tsubouchi
Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Hiroshi
H
Kiyonari
Protein Research Network, Yokohama 236-0004, Japan, and.
Akihiro
A
Iwamatsu
Department of Cell Biology, Japanese Foundation for Cancer Research, Cancer Institute, Tokyo 135-8550, Japan.
Tetsuo
T
Noda
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Hiroshi
H
Handa
Department of Medical Chemistry, Kansai Medical University, Moriguchi 570-8506, Japan.
Seiji
S
Ito
D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D018847:Opioid Peptides / Q000009:adverse effects / Q000494:pharmacology*; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000235:genetics
D000701:Analgesics, Opioid; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C113197:NIPSNAP1 protein, human; D009419:Nerve Tissue Proteins; C485133:Nipsnap1 protein, mouse; D018847:Opioid Peptides; D011506:Proteins; C111148:nocistatin