ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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, hSPRΔ325, differ in their desensitization and internalization. In HEK-293 cells expressing either hSPRΔ325 or hSPR, SP-induced desensitization of the two receptors was similar when measured by inositol triphosphate accumulation or by transient translocation of coexpressed PKCβII-GFP to the plasma membrane. Moreover, translocation of β-arrestin 1 or 2-GFP (βarr1-GFP or βarr2-GFP) to the plasma membrane, and receptor internalization were also similar. However, hSPR and hSPRΔ325 differ in their phosphorylation and in their ability to form β-arrestin-containing endocytic vesicles. Unlike hSPR, hSPRΔ325 is not phosphorylated to a detectable level in intact HEK293 cells, and whereas hSPR forms vesicles containing either βarr1-GFP or βarr2-GFP, hSPRΔ325 does not form any vesicles with βarr1-GFP, and forms fewer vesicles with βarr2-GFP. We conclude that truncated hSPR undergoes agonist-dependent desensitization and internalization without detectable receptor phosphorylation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2003.01577.x
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