Summary of the characteristics of the NT receptor subtypes
| Neurotensin N-Glu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-C | |||
|---|---|---|---|
| Neuromedin N N-Lys-Ile-Pro-Tyr-Ile-Leu-C | |||
| NT Receptor Subtypes | NT1 (NTRH) | NT2(NTRL) | NT3 (gp95/sortilin) |
| Cloned | • rNT1(Tanaka et al., 1990) • mNT1(Unpublished) • hNT1 (Vita et al., 1993; Watson et al., 1993) | • rNT2 (Chalon et al., 1996) • mNT2 (Mazella et al., 1996) • hNT2 (Vita et al., 1998) | • hNT3 (Mazella et al., 1998; Zsürger et al., 1994) |
| Gene characteristics | • hNT1 gene localized to long arm (20q13) of chromosome 20 • hNT1tetranucleotide repeat polymorphism 3 kb from gene • hNT1 polymorphism at amino acid 194 | • Two splice variants expressed in the CNS (604 and 423 bp). Only the 604 bp splice variant is expressed in glial cultures. | • hNT3 gene mapped to proximal short arm of chromosome 1 • hNT3-two NT3 mRNA transcripts (3.5 and 8.0 kb) expressed |
| Receptor size and alternative processing | • 50–60 kDa | • mNT2 = 45 kDa, 417 amino acids, alternative splice sight produces truncated receptor (282 amino acids, 5-transmembrane-spanning regions) expressed in spinal cord | • 100 kDa • Coexpression with furin (prohormone convertase) cleaves receptor to 95 kDa and changes NT affinity from 10–15 nM to 0.1–0.3 nM. |
| Receptor classification | • G-protein-coupled 7-transmembrane spanning regions | • G-protein-coupled 7-transmembrane-spanning regions | • Type I amino acid receptor single transmembrane-spanning region |
| Characteristics | • Located on neurons and glia | • Located on neurons and glia | • Expressed in neurons, glia, and adipocytes • Located on intracellular vesicles containing GLUT4 glucose transporter transported to the plasma membrane in response to insulin • NT triggers insertion of the receptor into the membrane from an intracellular compartment in mouse cortical neurons |
| Agonists | • NT (K
d= 0.1–0.3 nM) • NN • Xenopsin | • NT (K
d = 3–10 nM) • NN • Xenopsin • SR48692 (expressed in oocytes or CHO cells) • SR142948A (expressed in oocytes or CHO cells) • Levocabastine (expressed in oocytes or CHO cells) | • NT (K
d = 0.1–0.3 nM) • Receptor associated protein, a 40-kDa endoplasmic reticulum resident protein • Cleaved sortilin propeptide |
| Antagonists | SR48692 SR142948A | • NT (expressed in oocytes or CHO cells) • SR142948A • Levocabastine (weak agonist) looks like antagonism of NT effects | • Uncleaved sortilin propeptide functional antagonist blocks agonist binding until cleaved from receptor • SR48692 and SR142948A do not block NT binding in COS-7 cell extracts but block NT effects in cancer cell lines |
The amino acid sequence of NT and neuromedin N are provided in the top portion of the table. The lower section of the table summarizes the general characteristics, receptor agonists and antagonists for each of the three cloned NTRs (Chabry et al., 1993;Chalon et al., 1996; Gully et al., 1997;Hermans and Maloteaux, 1998; Le et al., 1997a; 1997b;Morris et al., 1998; Munck Petersen et al., 1999; Nouel et al., 1999; Petersen et al., 1997; Vincent, 1995; Vincent et al., 1999; Watson et al., 1993; Yamada et al., 1998).
rNT, rat NTR; mNT, mouse NTR; hNTR, human NTR.