Human substance P receptor lacking the C-terminal domain remains competent to desensitize and internalize

J Neurochem. 2003 Feb;84(4):854-63. doi: 10.1046/j.1471-4159.2003.01577.x.


Substance P receptor (SPR) and its naturally occurring splice-variant, lacking the C-terminal tail, are found in brain and spinal cord. Whether C-terminally truncated SPR desensitizes like full-length SPR is controversial. We used a multivaried approach to determine whether human SPR (hSPR) and a C-terminally truncated mutant, hSPRDelta325, differ in their desensitization and internalization. In HEK-293 cells expressing either hSPRDelta325 or hSPR, SP-induced desensitization of the two receptors was similar when measured by inositol triphosphate accumulation or by transient translocation of coexpressed PKCbetaII-GFP to the plasma membrane. Moreover, translocation of beta-arrestin 1 or 2-GFP (betaarr1-GFP or betaarr2-GFP) to the plasma membrane, and receptor internalization were also similar. However, hSPR and hSPRDelta325 differ in their phosphorylation and in their ability to form beta-arrestin-containing endocytic vesicles. Unlike hSPR, hSPRDelta325 is not phosphorylated to a detectable level in intact HEK293 cells, and whereas hSPR forms vesicles containing either betaarr1-GFP or betaarr2-GFP, hSPRDelta325 does not form any vesicles with betaarr1-GFP, and forms fewer vesicles with betaarr2-GFP. We conclude that truncated hSPR undergoes agonist-dependent desensitization and internalization without detectable receptor phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Arrestins / genetics
  • Cell Line
  • Green Fluorescent Proteins
  • Humans
  • Isoenzymes / genetics
  • Kidney / cytology
  • Kidney / metabolism
  • Luminescent Proteins / genetics
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Binding / physiology
  • Protein Isoforms / genetics
  • Protein Kinase C / genetics
  • Protein Kinase C beta
  • Protein Structure, Tertiary / physiology
  • Protein Transport / physiology
  • Receptors, Neurokinin-1 / drug effects
  • Receptors, Neurokinin-1 / genetics*
  • Receptors, Neurokinin-1 / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Substance P / pharmacology
  • Transfection
  • beta-Arrestin 1
  • beta-Arrestins


  • ARRB1 protein, human
  • Arrestins
  • Isoenzymes
  • Luminescent Proteins
  • Protein Isoforms
  • Receptors, Neurokinin-1
  • Recombinant Fusion Proteins
  • beta-Arrestin 1
  • beta-Arrestins
  • Green Fluorescent Proteins
  • Substance P
  • Protein Kinase C
  • Protein Kinase C beta